beta-endorphin and Body-Weight

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Pressure; Body Weight; Circadian Rhythm; Female; Humans; Hydrocortisone; Hypertension; Male; Obesity

Since the second decade of this century it has been known that opiates can influence ingestive behaviors. Generally, opioid agents enhance feeding and opioid antagonists decrease feeding. The present paper reviews the responsiveness of different animal species to opiates in relation to ingestive behaviors, the opioid receptors involved in such consummatory behaviors, the site of action of opioid modulation of feeding, the role of glucose in opioid induced feeding, and endocrine effects on opioid feeding systems. We emphasize the finding that more than one opioid receptor is involved in the modulation of feeding. A large body of evidence indicates a major role for the dynorphin/alpha-neo-endorphin kappa opioid receptor as one of the receptors involved in feeding modulation. Opioids appear to exert their effect predominantly within the central nervous system, though peripheral effects on taste and gastrointestinal function may play a role in opioid-induced feeding. Although opioid blockade acutely blocks food intake, chronic administration of opiate antagonists to humans and laboratory animals has not proven to be an effective means of decreasing body weight. Chronic opiate administration decreases body weight and autosensitization of beta-endorphin increases body weight. Thus, although it is clear that opioids can effect food intake, it is not clear what effect chronic administration of opioids has no food intake or body weight.

Topics: Adrenal Cortex Hormones; Animals; beta-Endorphin; Body Weight; Brain Chemistry; Drinking Behavior; Endorphins; Feeding Behavior; Glucose; Gonadal Steroid Hormones; Humans; Narcotics; Rats; Receptors, Opioid; Time Factors

Anorexia nervosa (AN) is a debilitating eating disorder characterized by severely restricted eating and significant body weight loss. In addition, many individuals also report engaging in excessive exercise. Previous research using the activity-based anorexia (ABA) model has implicated the hypothalamic proopiomelanocortin (POMC) system. Using the ABA model,

Topics: Animals; Anorexia; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Body Weight; Food; Hypothalamus; Mice; Neurons; Pro-Opiomelanocortin

Acute pain and peripheral sensitization development after cautery disbudding was investigated in 33 calves administered preventive multimodal analgesia. The animals were assigned randomly to three groups: 1) Group SH (Control), undergoing sham disbudding at 1 and 4weeks of age; 2) Group ED (Early Disbudding), undergoing disbudding at 1week of age and sham disbudding at 4weeks of age; 3) Group LD (Late Disbudding), undergoing sham disbudding at 1week of age and disbudding at 4weeks of age. Physiological parameters (heart rate, respiratory rate, rectal temperature, invasive blood pressure, cortisol, β-endorphin, interleukin-1β, interleukin-6, tumor necrosis factor-α and haptoglobin plasmatic concentration), local variables (tactile sensitivity score, pressure pain thresholds and horn temperature), behavior and pain scores [multidimensional pain scale and visual analogue scale (VAS)] were assessed at baseline and at several pre-determined time points until 24h after disbudding. Tactile sensitivity score significantly and equally increased in both groups ED and LD and pressure pain thresholds significantly decreased in group LD until 24h after disbudding compared to group SH. Pain and VAS scores significantly and equally increased in both groups ED and LD until 24h after disbudding compared to group SH. No significant differences in physiological parameters, behavior and horn temperature were detected among groups. The present study suggests that acute pain and peripheral sensitization develop and do not differ in calves disbudded at 1week and 4weeks of age. Moreover, the use of physiological and behavioral parameters as sole indicators of acute pain might lead to improper conclusions and should be reassessed.

Topics: Acute Pain; Aging; Animals; beta-Endorphin; Blood Pressure; Body Temperature; Body Weight; Cattle; Cautery; Haptoglobins; Heart Rate; Horns; Hydrocortisone; Pain Measurement; Pain Threshold; Prospective Studies; Random Allocation; Respiration; Retrospective Studies; RNA, Messenger; Touch Perception; Tumor Necrosis Factor-alpha

Topics: Animals; beta-Endorphin; Body Weight; Cell Line; Corticosterone; Cyclooxygenase 2; Eating; Macrophages; Malondialdehyde; Mentha; Mice; Mitogen-Activated Protein Kinases; Nitric Oxide; Plant Extracts; Psychotropic Drugs; Rats; Rats, Sprague-Dawley; Restraint, Physical; Serotonin; Stress, Psychological

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medical amino acid widely used as an anti-inflammatory and a whitening agent. This study examined the effect of tranexamic acid administration in wrinkle formation following skin dryness. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In these NOA mice, deterioration of transepidermal water loss (TEWL), generation of wrinkles, decrease of collagen type I, and increases in mast cell proliferation and tryptase and matrix metalloproteinase (MMP-1) release were observed. However, these symptoms were improved by tranexamic acid treatment. Moreover, the increase in the β-endorphin level in the blood and the expression of μ-opioid receptor on the surface of fibroblasts increased by tranexamic acid treatment. In addition, when the fibroblasts induced by tranexamic acid treatment were removed, the amelioration effect by tranexamic acid treatment was halved. On the other hand, tranexamic acid treated NOA mice and mast cell removal in tranexamic acid treated NOA mice did not result in changes in the wrinkle amelioration effect. Additionally, the amelioration effect of mast cell deficient NOA mice was half that of tranexamic acid treated NOA mice. These results indicate that tranexamic acid decreased the proliferation of mast cells and increases the proliferation of fibroblasts, subsequently improving wrinkles caused by skin dryness.

Topics: Adrenocorticotropic Hormone; Aminoquinolines; Animals; Antibodies; Benzamides; beta-Endorphin; Body Weight; Cell Proliferation; Chloroquine; Corticosterone; Immunoglobulin E; Male; Mast Cells; Mice; Receptors, Opioid, mu; Skin Aging; Skin Diseases; Stem Cell Factor; Tranexamic Acid; Water Loss, Insensible

Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight.

Topics: Animals; Appetite; beta-Endorphin; Body Weight; Case-Control Studies; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Enkephalins; Feeding Behavior; Female; Food Deprivation; Male; Mice; Mice, Knockout; Obesity; Protein Precursors; Sucrose

The production of bioactive peptides from biologically inactive precursors involves extensive post-translational processing, including enzymatic cleavage by proteolytic peptidases. Endoproteolytic prohormone-convertases initially cleave the precursors of many neuropeptides at specific amino acid sequences to generate intermediates with basic amino acid extensions on their C-termini. Subsequently, the related exopeptidases, carboxypeptidases D and E (CPD and CPE), are responsible for removing these amino acids before the peptides achieve biological activity. We investigated the effect of photoperiod on the processing of the neuropeptide precursor pro-opiomelanocortin (POMC) and its derived neuropeptides, α-melanocyte-stimulating hormone (MSH) and β-endorphin (END), within the hypothalamus of the seasonal Siberian hamster (Phodopus sungorus). We thus compared hypothalamic distribution of CPD, CPE, α-MSH and β-END using immunohistochemistry and measured the enzyme activity of CPE and concentrations of C-terminally cleaved α-MSH in short-day (SD; 8 : 16 h light/dark) and long-day (LD; 16 : 8 h light/dark) acclimatised hamsters. Increased immunoreactivity (-IR) of CPE, as well as higher CPE activity, was observed in SD. This increase was accompanied by more β-END-IR cells and substantially higher levels of C- terminally cleaved α-MSH, as determined by radioimmunoassay. Our results suggest that exoproteolytic cleavage of POMC-derived neuropeptides is tightly regulated by photoperiod in the Siberian hamster. Higher levels of biological active α-MSH- and β-END in SD are consistent with the hypothesis that post-translational processing is a key event in the regulation of seasonal energy balance.

Topics: alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Body Weight; Carboxypeptidase H; Cricetinae; Male; Neuropeptides; Phodopus; Photoperiod; Pro-Opiomelanocortin; Protein Processing, Post-Translational; Seasons; Substrate Specificity

Opioid peptide β-endorphin (β-EP) plays a modulatory role in vertebrate reproduction. However, the role of opioid peptides in reproductive stress response is least understood in fishes. The aim of the present study was to determine the effect of different doses of β-EP on luteinizing hormone (LH) secretion in normal and the opioid receptor antagonist naltrexone (NALT) in stressed female tilapia Oreochromis mossambicus. Administration of 4 μg β-EP, but not 0.5 or 1.5 μg β-EP, daily for 22 days caused suppression of LH-secreting cells at the proximal pars distalis of the pituitary gland, concomitant with a significant reduction in the mean GSI and HSI in 4 μg β-EP-treated fish compared to controls. On the other hand, exposure of the fish to mild acute stressors for 22 days caused changes in the LH-secreting cells similar to that of high dose of β-EP, whereas administration of NALT attenuated these effects. Taken together, the results indicate that increased concentration of β-EP as may occur during stressful conditions can cause suppression of LH secretion, leading to the inhibition of spawning, and that treatment of NALT attenuates the stress-induced inhibition of LH secretion in fish.

Topics: Analysis of Variance; Animals; beta-Endorphin; Body Weight; Dose-Response Relationship, Drug; Female; Gonads; Immunohistochemistry; India; Liver; Luteinizing Hormone; Naltrexone; Organ Size; Pituitary Gland; Reproduction; Stress, Physiological; Tilapia

Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injection of β-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv β-EP infusion. In the next study, a subthreshold dose of β-EP was injected together with Nle(4), d-Phe(7) (NDP)-MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of β-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4-7, β-EP no longer blocked these effects. Of note, the stimulatory effect of β-EP on feeding and its ability to antagonize MSH were specific for β-EP(1-31) and were not observed with β-EP(1-27). This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance.

Topics: alpha-MSH; Animals; beta-Endorphin; Body Weight; Eating; Male; Rats; Rats, Sprague-Dawley

Epidemiological studies suggest that maternal undernutrition predisposes the offspring to development of energy balance metabolic pathologies in adulthood. Using a model of a prenatal maternal 70% food-restricted diet (FR30) in rats, we evaluated peripheral parameters involved in nutritional regulation, as well as the hypothalamic appetite-regulatory system, in nonfasted and 48-h-fasted adult offspring. Despite comparable glycemia in both groups, mild glucose intolerance, with a defect in glucose-induced insulin secretion, was observed in FR30 animals. They also exhibited hyperleptinemia, despite similar visible fat deposits. Using semiquantitative RT-PCR, we observed no basal difference of hypothalamic proopiomelanocortin (POMC) and neuropeptide Y (NPY) gene expression, but a decrease of the OB-Rb and an increase of insulin receptor mRNA levels, in FR30 animals. These animals also exhibited basal hypercorticosteronemia and a blunted increase of corticosterone in fasted compared with control animals. After fasting, FR30 animals showed no marked reduction of POMC mRNA levels or intensity of beta-endorphin-immunoreactive fiber projections. By contrast, NPY gene expression and immunoreactive fiber intensity increased. FR30 rats also displayed subtle alterations of food intake: body weight-related food intake was higher and light-dark phase rhythm and refeeding time course were modified after fasting. At rest, in the morning, hyperinsulinemia and a striking increase in the number of c-Fos-containing cells in the arcuate nucleus were observed. About 30% of the c-Fos-expressing cells were POMC neurons. Our data suggest that maternal undernutrition differently programs the long-term appetite-regulatory system of offspring, especially the response of POMC neurons to energy status and food intake rhythm.

Topics: Animals; Appetite; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Body Composition; Body Weight; Eating; Energy Metabolism; Feeding Behavior; Female; Fetal Nutrition Disorders; Genes, fos; Glucose Tolerance Test; Hormones; Insulin; Litter Size; Male; Neurons; Neuropeptide Y; Pregnancy; Prenatal Exposure Delayed Effects; Pro-Opiomelanocortin; Rats; Rats, Wistar; Receptor, Insulin; Receptors, Leptin

Ghrelin, an endogenous growth hormone secretagogue, is a known accelerator of feeding behavior and suppresses pulsatile secretion of luteinizing hormone (LH) in ovariectomized rats. However, the mechanisms underlying this action remain unclear. We examined the effects of naloxone (NAL), a specific opioid antagonist, on the suppression of pulsatile LH secretion by ghrelin to determine whether beta-endorphin (beta-END) is involved in this suppressive effect.. Ghrelin was administered intracerebroventricularly, and NAL was injected intravenously in ovariectomized rats; then, serum LH concentrations were measured by radioimmunoassay in blood samples drawn every 6 min for 2 h to analyze pulsatile secretion.. Administration of ghrelin significantly reduced mean LH concentration and pulse frequency. Coadministration of NAL with ghrelin significantly restored mean LH concentration and pulse frequency.. Suppressive effect of intracerebroventricular injection of ghrelin on pulsatile LH secretion was mediated by beta-END, suggesting that hypothalamic ghrelin suppressed pulsatile gonadotropin-releasing hormone secretion via beta-END in female rats.

Topics: Animals; beta-Endorphin; Body Weight; Catheterization; Female; Ghrelin; Hypothalamus; Luteinizing Hormone; Naloxone; Narcotic Antagonists; Ovariectomy; Radioimmunoassay; Rats; Rats, Wistar; Time Factors

Experimental evidence indicates that the endogenous opioid system influences stress responses as well as reinforces effects of addictive drugs. Because stress is an important factor contributing to drug dependence and relapse, we have now studied ethanol preference in enkephalin- and beta-endorphin-deficient mice under baseline conditions and after stress exposure.. In the present study we used a two-bottle choice paradigm to study ethanol consumption and stress-induced ethanol preference. To examine alcohol withdrawal symptoms the forced drinking procedure was employed. We performed an association analysis in two case-control samples of alcohol addicts to determine whether these opioid peptides also contribute to ethanol dependence in humans.. Ethanol consumption was significantly reduced in the absence of beta-endorphins, particularly in female knockout animals. Stress exposure results in an increased ethanol consumption in wild-type mice but did not influence ethanol-drinking in beta-endorphin knockouts. Enkephalin-deficient mice showed no difference from wild-type mice in baseline ethanol preference but also showed no stress-induced elevation of ethanol consumption. Interestingly, we found a two-marker haplotype in the POMC gene that was associated with alcohol dependence in females in both cohorts.. Together these results indicate a contribution of beta-endorphin to ethanol consumption and dependence.

Topics: Adult; Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Body Weight; Choice Behavior; Disease Models, Animal; Enkephalins; Female; Food Preferences; Gene Frequency; Genotype; Humans; Linkage Disequilibrium; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Polymorphism, Single Nucleotide; Pro-Opiomelanocortin; Sex Characteristics; Stress, Psychological

Both obesity and increased endorphin production are associated with an increase in blood pressure. We have previously demonstrated that the acute and chronic central nervous system (CNS) administration of beta-endorphin can increase or decrease blood pressure, respectively. Also high fat (HF) diet-induced obesity is associated with increased hypothalamic mu opioid receptors and increased blood pressure in response to ss-endorphins. In this study we investigated the effect of high fat diet-induced obesity on blood pressure, heart rate, and physical activity as well as determined the effect of mu opioids in unanesthetized rats. Male Wistar rats were implanted with a radiotelemetry transmitter to record cardiovascular dynamics and activity. They were fed either a HF diet (HF; 59% fat by caloric content, soy bean oil) or regular chow (control; 12% fat by caloric content). HF rats had higher body weights and their total caloric intake was greater than controls. The systolic blood pressures (SBP) were greater in the HF-obese rats. After 12-13 weeks the rats were infused chronically with a mu opioid agonist (D)-Ala(2), N-Me-Phe(4), Gly(5)-ol]-ENKEPHALIN (DAMGO) or a mu opioid antagonist ss-funaltrexamine (beta-FNA) via intracerebroventricular cannula. DAMGO increased the SBP and heart rate in controls, but not in HF obese rats. DAMGO did not affect physical activity; beta-FNA decreased SBP and increased HR in controls. We concluded that HF rats consumed more calories, gained more weight, and had higher SBP. However, the responsiveness to the mu-receptor agonist was not higher in the HF rats.

Topics: Animals; beta-Endorphin; Blood Pressure; Body Weight; Consciousness; Dietary Fats; Disease Models, Animal; Follow-Up Studies; Heart Rate; Male; Motor Activity; Neurotransmitter Agents; Obesity; Rats; Rats, Wistar; Receptors, Opioid, mu

A remarkable feature of the seasonal adaptation displayed by the Siberian hamster (Phodopus sungorus) is the ability to decrease food intake and body weight (by up to 40%) in response to shortening photoperiod. The regulating neuroendocrine systems involved in this adaptation and their neuroanatomical and molecular bases are poorly understood. We investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3) and 2 (PC2) and the endoproteolytic processing of the neuropeptide precursor pro-opiomelanocortin (POMC) within key energy balance regulating centres of the hypothalamus. We compared mRNA levels and protein distribution of PC1/3, PC2, POMC, adrenocorticotrophic hormone (ACTH), alpha-melanocyte-stimulating hormone (MSH), beta-endorphin and orexin-A in selected hypothalamic areas of long day (LD, 16:8 h light:dark), short day (SD, 8:16 h light:dark) and natural-day (ND, photoperiod depending on time of the year) acclimated Siberian hamsters. The gene expression of PC2 was significantly higher within the arcuate nucleus (ARC, P < 0.01) in SD and in ND (versus LD), and is reflected in the day length profile between October and April in the latter. PC1/3 gene expression in the ARC and lateral hypothalamus was higher in ND but not in SD compared to the respective LD controls. The immunoreactivity of PC1/3 cleaved neuropeptide ACTH in the ARC and PC1/3-colocalised orexin-A in the lateral hypothalamus were not affected by photoperiod changes. However, increased levels of PC2 mRNA and protein were associated with higher abundance of the mature neuropeptides alpha-MSH and beta-endorphin (P < 0.01) in SD. This study provides a possible explanation for previous paradoxical findings showing lower food intake in SD associated with decreased POMC mRNA levels. Our results suggest that a major part of neuroendocrine body weight control in seasonal adaptation may be effected by post-translational processing mediated by the prohormone convertases PC1/3 and PC2, in addition to regulation of gene expression of neuropeptide precursors.

Topics: Adaptation, Physiological; Adrenocorticotropic Hormone; alpha-MSH; Animals; beta-Endorphin; Body Weight; Cricetinae; Female; Gene Expression Regulation, Enzymologic; Hypothalamic Area, Lateral; Intracellular Signaling Peptides and Proteins; Male; Neuropeptides; Orexins; Phodopus; Photoperiod; Pro-Opiomelanocortin; Proprotein Convertase 1; Proprotein Convertase 2; Protein Precursors; Protein Processing, Post-Translational; RNA, Messenger; Seasons

Constitutional delay of puberty (CDP), a rare condition among girls, manifests as retarded sexual maturity past the 13th year of life. The clinical and endocrinological aspects of this interesting problem appear to have escaped attention in the literature. The purpose of the present study was to compare body composition and concentrations of leptin, neuropeptide Y (NPY), beta-endorphin, growth hormone (GH), insulin growth factor-I (IGF-I) and insulin at menarche in CDP girls and girls with normal pubertal development (NP).. We enrolled 11 girls with CDP and 40 girls with NP. All participants were studied at or within 3 months of menarche. Age, height and weight were recorded. Body composition was established with a body composition analyzer. Radioimmunoassays were performed to measure concentrations of NPY, beta-endorphin, leptin, GH, IGF-I and insulin.. The mean age at menarche in the CDP and NP groups was 16.1 and 12.5 years, respectively (p = 0.0001). CDP girls at menarche were taller (1.64 vs. 1.57 m; p = 0.012). The difference between groups in body weight (57.5 vs. 50.4 kg; p = 0.1), body mass index (BMI), fat mass, fat percentage (BF%) and lean mass was not significant, and nor was the difference in leptin, GH and insulin levels. However, CDP girls demonstrated significantly higher NPY concentrations (199.4+/-105.1 vs. 56.9+/-26.3 pg/ml; p = 0.001). NPY correlated with BF% (r = 0.60) in this group. IGF-I concentrations were significantly lower in CDP girls (524.8+/-50.6 ng/ml) than in NP girls (744.5+/-56.1 ng/ml; p = 0.024).. Girls with CDP differed from NP girls only in age at menarche and height; they did not differ significantly with respect to BMI and body composition parameters. Higher concentrations of NPY in CDP girls may be responsible for CDP and reduced levels of IGF-I. Correlation of NPY with BF% suggests an involvement of this neuropeptide in the process of fat accumulation associated with CDP.

Topics: Adipose Tissue; Adolescent; beta-Endorphin; Body Composition; Body Height; Body Mass Index; Body Weight; Child; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Menarche; Neuropeptide Y; Puberty, Delayed

The present study was performed to examine the role of the endogenous beta-endorphinergic system on blood pressure regulation, sympathetic and brain activity during body sodium overload. Beta-endorphin knockout (beta end-/-), heterozygous (beta end+/-) and wild-type (beta end+/+) mice were submitted for two weeks to either a normal- or a high-sodium diet (NSD and HSD, respectively), and systolic blood pressure (SBP), urinary catecholamines (as an index of sympathetic nervous system activity), and the brain pattern of Fos-like immunoreactivity (as a marker of neuronal activation) were evaluated in each group. HSD caused a significant increase in SBP in beta end-/- mutant mice compared with beta end+/+ mice kept in the same experimental conditions (P < 0.01), but no statistical differences were observed between beta end+/- and beta end+/+ on a HSD. Moreover, when animals from the three genetic lines were fed with a NSD no changes in SBP were evidenced. With regard to brain activity, beta end-/- mice maintained on a HSD showed a significant increase in Fos-like immunoreactive neurons in the median preoptic nucleus (P < 0.01) compared with beta end+/- and beta end+/+ animals. Additionally, beta end-/- mice had higher levels of urinary epinephrine excretion (P < 0.05) on a HSD in comparison to beta end+/+ and beta end+/- animals in the same experimental conditions. No differences, however, were registered in norepinephrine and dopamine urinary excretion in animals from the three genetic lines after two weeks on either a HSD or a NSD. In summary, our results indicate that the beta-endorphinergic system may play a part in the compensatory response to sodium overload, since the absence of beta-endorphin causes an increase in systolic blood pressure, and increases median preoptic nucleus neural activity and urinary epinephrine excretion.

Topics: Analysis of Variance; Animals; Behavior, Animal; beta-Endorphin; Blood Pressure; Body Weight; Brain; Catecholamines; Creatinine; Drinking; Gene Expression Regulation; Immunohistochemistry; Mice; Mice, Knockout; Proto-Oncogene Proteins c-fos; Sodium, Dietary

The main goal of the present experiment was to study the voluntary consumption of alcohol before and after a single injection of estradiol valerate (EV); another goal was to assess beta-endorphin (beta-EP) neurons and beta-EP peptide in hypothalamic arcuate nucleus 10 weeks after the injection of EV. Wistar female rats were injected either with a single 2.0 mg/rat injection of EV or with 0.2 ml of corn oil/rat (vehicle group). Two weeks before the injection and 10 weeks after it, every other day both groups were exposed to a free-choice alcohol drinking procedure. In weeks 4 and 5, the post-injection-consumption of alcohol was higher in the EV group than the vehicle group. In the EV group, food intake decreased and coincided with body weight lost in week 1 of post-EV injection. EV treated females showed significantly lower number of beta-EP neurons than control group (reduction of 51.22%); however, beta-EP content was similar in both groups, and they did not differ in the number of TSH and LHRH neurons. The present results suggest a positive relationship between high alcohol consumption and possible initial deficiency of beta-endorphin content. The transient increase in alcohol consumption suggests a possible compensatory secretory effect of the surviving beta-endorphinergic neurons, particularly when they are chronically stimulated with alcohol.

Topics: Alcohol Drinking; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Body Weight; Estradiol; Female; Immunohistochemistry; Neurons; Rats; Rats, Wistar

Fasting attenuates disease-associated anorexia, but the mechanisms underlying this effect are not well understood. In the present study, we investigated the extent to which a 48 h fast alters hypothalamic neuronal activity in response to the anorectic effects of lipopolysaccharide in rats. Male rats were fed ad libitum or fasted, and were injected with i.p. saline or lipopolysaccharide (250 microg/kg). Immunohistochemistry for Fos protein was used to visualize neuronal activity in response to lipopolysaccharide within selected hypothalamic feeding regulatory nuclei. Additionally, food intake, body weight, plasma interleukin-1 and leptin levels, and the expression of mRNA for appetite-related neuropeptides (neuropeptide Y, proopiomelanocortin and cocaine-amphetamine-regulated transcript) were measured in a time-related manner. Our data show that the pattern of lipopolysaccharide-induced Fos expression was similar in most hypothalamic nuclei whatever the feeding status. However, we observed that fasting significantly reduced lipopolysaccharide-induced Fos expression in the paraventricular nucleus, in association with an attenuated lipopolysaccharide-induced anorexia and body weight loss. Moreover, lipopolysaccharide reduced fasting-induced Fos expression in the perifornical area of the lateral hypothalamus. Lipopolysaccharide-induced circulating levels of interleukin-1 were similar across feeding status. Finally, fasting, but not lipopolysaccharide, affected circulating level of leptin and appetite-related neuropeptides expression in the arcuate nucleus. Together, our data show that fasting modulates lipopolysaccharide-induced anorexia and body weight loss in association with neural changes in specific hypothalamic nuclei.

Topics: Animals; Anorexia; Behavior, Animal; beta-Endorphin; Body Weight; Cell Count; DNA-Binding Proteins; Eating; Enzyme-Linked Immunosorbent Assay; Feeding Behavior; Food Deprivation; Gene Expression Regulation; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Interleukin-1; Interleukin-1beta; Leptin; Lipopolysaccharides; Male; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Oncogene Proteins v-fos; Peptide Fragments; Pro-Opiomelanocortin; Rats; Rats, Wistar; STAT3 Transcription Factor; Time Factors; Trans-Activators

Beta-endorphin is an endogenous opioid peptide that is released during stress and has been associated with many physiological functions. In this experiment beta-endorphin deficient mice were used to study the role of endorphins in the acute physiological and behavioral responses to a social conflict, as well as their role in social stress-induced changes in sleep. Adult male beta-endorphin deficient and wild type mice were subjected to the stress of a 1 h social conflict with an aggressive dominant conspecific. After the conflict, the beta-endorphin deficient mice had higher corticosterone levels but the peak increase in body temperature was not different from that in wild type animals. In fact, body temperature returned to baseline levels faster in the beta-endorphin deficient mice. During their interaction with the aggressive conspecific several of the beta-endorphin deficient mice showed clear signs of counter aggression whereas this was not seen in any of the wild type mice. Overall, the beta-endorphin deficient mice and wild type mice had fairly similar sleep patterns under baseline conditions and also showed similar amounts of NREM sleep, REM sleep and EEG slow-wave energy after the social conflict. In addition, no differences were found in the sleep patterns of mice that showed counter aggression and mice that did not. In conclusion, the results suggest that beta-endorphin modulates the acute endocrine, thermoregulatory and behavioral response to a social conflict but the data do not support a major role for beta-endorphin in the regulation of sleep or social stress-induced alterations in sleep.

Topics: Aggression; Animals; Behavior, Animal; beta-Endorphin; Body Temperature; Body Weight; Conflict, Psychological; Corticosterone; Electroencephalography; Female; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Sleep; Time Factors

Feeding behavior can be divided into appetitive and consummatory phases, differing in neural substrates and effects of deprivation. Opioids play an important role in the appetitive aspects of feeding, but they also have acute stimulatory effects on food consumption. Because the opioid peptide beta-endorphin is co-synthesized and released with melanocortins from proopiomelanocortin (POMC) neuronal terminals, we examined the physiological role of beta-endorphin in feeding and energy homeostasis using a strain of mutant mice with a selective deficiency of beta-endorphin. Male beta-endorphin-deficient mice unexpectedly became obese with ad libitum access to rodent chow. Total body weight increased by 15% with a 50-100% increase in the mass of white fat. The mice were hyperphagic with a normal metabolic rate. Despite the absence of endogenous beta-endorphin, the mutant mice did not differ from wild-type mice in their acute feeding responses to beta-endorphin or neuropeptide Y administered intracerebroventricularly or naloxone administered intraperitoneally. Additional mice were studied using an operant behavioral paradigm to examine their acquisition of food reinforcers under increasing work demands. Food-deprived, beta-endorphin-deficient male mice emitted the same number of lever presses under a progressive ratio schedule compared to wild-type mice. However, the mutant mice worked significantly less than did the wild-type mice for food reinforcers under nondeprived conditions. Controls for nonspecific effects on acquisition of conditioned learning, activity, satiety, and resistance to extinction revealed no genotype differences, supporting our interpretation that beta-endorphin selectively affects a motivational component of reward behavior under nondeprived conditions. Therefore, we propose that beta-endorphin may function in at least two primary modes to modulate feeding. In the appetitive phase, beta-endorphin release increases the incentive value of food as a primary reinforcer. In contrast, it appears that endogenous beta-endorphin may inhibit food consumption in parallel with melanocortins and that the orexigenic properties previously ascribed to it may actually be due to other classes of endogenous opioid peptides.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Brain; Conditioning, Operant; Dynorphins; Eating; Energy Metabolism; Enkephalins; Feeding Behavior; Female; Homeostasis; Male; Mice; Mice, Knockout; Pro-Opiomelanocortin

The present study examined the interrelationships between feeding responses produced by mu opioid receptor agonists and melanocortin-3 or 4 (MC-3/4) receptor antagonists. Feeding induced by the mu-sensitive opioid peptide, beta-endorphin (betaEND, 10 microg, i.c.v.) was significantly and dose-dependently reduced by pretreatment with the MC-3/4 receptor agonist, melanotan-II (MTII: 0.01-10 nmol, i.c.v.). Moreover, the selective mu opioid antagonist, beta-funaltrexamine (betaFNA: 2-20 mug, i.c.v.), significantly and dose-dependently reduced feeding and weight gain elicited by the potent MC-3/4 receptor antagonist, SHU-9119 (0.5 nmol, i.c.v.), especially at those intake periods (24-48 h) when SHU-9119 produced maximal ingestive effects. These data extend previous findings demonstrating interactions between opioid and melanocortin receptors in the mediation of food intake.

Topics: Animals; beta-Endorphin; Body Weight; Dose-Response Relationship, Drug; Eating; Male; Melanocyte-Stimulating Hormones; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Melanocortin; Receptors, Opioid, mu

A series of experiments investigated the effects of a single injection of estradiol valerate (EV) on female rats' consumption of alcoholic beverages. EV provides sustained release of estradiol. Just after an injection of EV, rats' intake of a palatable alcoholic beverage, which had been taken regularly before, is reduced dramatically. Subsequently, rats' intake of alcoholic beverage returns to baseline levels. With continued opportunity to drink, rats take more ethanol than controls. When EV was given 15 and 31 days before the first opportunity to drink an alcoholic beverage, female rats markedly enhanced their intake of ethanol. Once enhanced intakes emerged, they were observed with different kinds of alcoholic beverages and endured for months.

Topics: Alcohol Drinking; Alcoholic Beverages; Animals; Behavior, Addictive; beta-Endorphin; Body Weight; Dose-Response Relationship, Drug; Estradiol; Female; Injections, Intramuscular; Male; Rats; Rats, Sprague-Dawley; Taste

The role of beta-endorphin (beta-EP) in ethanol-altered NK cell cytolytic activity is studied using male Fischer-344 rats as an animal model. Ethanol was administered for 1, 2, 3, or 4 wk in a liquid diet containing 8.7% ethanol (v/v), which means that 37% of the total calories were derived from ethanol. Rats treated with ethanol for 1 wk showed an increase in hypothalamic and plasma levels of immunoreactive (IR)-beta-EP, but displayed no significant effect on NK cell activity determined by (51)Cr release assay, as compared with those in pair-fed and ad libitum-fed animals. However, animals treated with ethanol for 2, 3, or 4 wk showed decreased hypothalamic and plasma levels of IR-beta-EP and decreased splenic NK cell activity. No significant decrease in the number of splenocytes and NK cells or in the percentage of NK cells was seen until after 3 and 4 wk of ethanol treatment. Exposure in vitro of splenic lymphocytes obtained from control animals to various concentrations of beta-EP increased NK cell activity. The opiate antagonist naltrexone blocked the beta-EP-stimulated effect. The in vitro NK cell response to beta-EP was reduced in the splenocytes obtained from animals treated with ethanol for 2 wk, but not in those obtained from animals treated with ethanol for 1 wk as compared with those in control animals. Additionally, beta-EP administration into the paraventricular nucleus of the hypothalamus stimulated NK cell cytolytic activity, whereas the opiate blocker administration reduced NK cell activity. The NK cell responses to paraventricular nucleus beta-EP were reduced in the animals treated with ethanol for 2 wk. These data provide evidence for the first time that ethanol inhibits NK cell cytolytic activity, possibly by reducing beta-EP-regulated splenic NK cell function.

Topics: Animals; Antibodies; beta-Endorphin; Body Weight; Cells, Cultured; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Ethanol; Hypothalamus; Killer Cells, Natural; Lymphocyte Count; Male; Naltrexone; Narcotic Antagonists; Rats; Rats, Inbred F344; Spleen; Tumor Cells, Cultured

Obesity in normal animals has been demonstrated to be associated with a decrease in sensitivity to leptin especially as it relates to leptin's capacity to increase sympathetic nerve activity and enhance cardiovascular dynamics. In normal animals leptin has been demonstrated to exert significant regulatory responses by its capacity to increase proopiomelanocortin (POMC) expression and especially the increase in alpha melanocyte stimulating hormone (alphaMSH). These responses to leptin are blocked by a melanocortin-4 (MC-4) receptor antagonist. In this study we investigated the responsiveness of the sympathetic nervous system and cardiovascular system of high fat fed obese animals to the intracerebroventricular (ICV) administration of the POMC products alphaMSH and beta-endorphin (beta-END). We further investigated these responses in obese animals following leptin administration in the presence of MC-4 receptor and opioid receptor blockade. The ICV administration of leptin resulted in an increase in lumbar sympathetic nerve activity (LSNA) and mean arterial pressure (MAP) in normals but decreased it in the obese. The ICV administration of alphaMSH increased the LSNA and MAP in normal animals but to a lesser degree in obese animals. On the other hand beta-endorphin decreased the LSNA and MAP in normal animals but increased it in obese animals. Additionally ICV leptin administration in obese animals in the presence of MC-4 or opioid receptor blockade resulted in an increase in sympathetic activity and a pressor response. From these studies we conclude that obesity in high fat fed animals is characterized by a decreased sensitivity to alphaMSH and a paradoxical response to beta-endorphin and this altered responsiveness may be a factor in the altered leptin resistance characteristic of obese animals.

Topics: Agouti Signaling Protein; alpha-MSH; Animals; beta-Endorphin; Blood Pressure; Body Weight; Dietary Fats; Drug Resistance; Electrophysiology; Female; Heart Rate; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Leptin; Naloxone; Narcotic Antagonists; Obesity; Pressoreceptors; Pro-Opiomelanocortin; Proteins; Rats; Rats, Wistar; Receptor, Melanocortin, Type 4; Receptors, Corticotropin; Receptors, Opioid; Splanchnic Nerves

A number of recent studies suggest that interleukin 1 beta (IL-1 beta) is a major mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious aggression. We investigated whether IL-1 beta mediates long-term changes in HPA activity and studied the cellular regulation of the anterior pituitary. To mimic chronically elevated IL-1 beta production thought to occur during infectious diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of male rats and hIL-1 beta was infused continuously at rates of 1 or 3 micrograms/day. Effects of hIL-1 beta action on plasma ACTH, beta-endorphin (beta-EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and beta-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP, CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified using a highly sensitive solution hybridization nuclease protection assay. Continuous infusion of hIL-1 beta stimulated the HPA axis at varying degrees. Increased HT CRH gene expression, AP POMC gene transcription, ACTH and beta-EP release occurred only during the first 3 days of the treatment. A long-lasting enhancement of ACTH and beta-EP synthesis and of POMC gene expression resulted from activated POMC gene transcription followed by an increased POMC mRNA stability and decreased POMC mRNA turnover. In the AP, stimulation of ACTH and beta-EP secretion and POMC gene transcription disappeared after continuous IL-1 beta treatment, possibly in part due to a refractory process mediated by decreased CRH-Rc gene expression in corticotropes.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Gene Expression; Hypothalamus; Infusions, Parenteral; Interleukin-1; Male; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; RNA, Messenger

Sulfated glycoprotein-2 (SGP-2 or clusterin) is a complex multifunctional molecule that has been recently been implicated in neuronal degeneration and remodeling. We have shown that estradiol treatment results in a selective destruction of beta-endorphin neurons in the hypothalamic arcuate nucleus. We have used immunocytochemistry to determine the distribution of SGP-2 immunoreactivity in the rat hypothalamus and to assess the effects of the estradiol-induced destruction of beta-endorphin neurons on SGP-2 expression. We have found that SGP-2-immunopositive neurons normally occur in the medial preoptic area (MPOA), supraoptic nucleus (SON), paraventricular nucleus (PVN), dorsomedial nucleus (DM), and the lateral hypothalamic area (LHA) in both males and females. The neuropil appears free of label. Treatment with estradiol valerate results in the appearance of immunopositive punctate deposits in the neuropil in the MPOA, PVN and DM. The number and distribution of SGP-2-positive neurons are unaffected by estradiol treatment except in the MPOA, where there are twice as many SGP-2-positive neurons as in controls. These effects are precluded by treatment with vitamin E, with blocks the cytotoxic action of estradiol on beta-endorphin neurons. Thus, we interpret these changes as responses to the loss of beta-endorphin afferents.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Body Weight; Clusterin; Estradiol; Estrus; Female; Glycoproteins; Hypothalamic Diseases; Hypothalamus; Immunohistochemistry; Male; Molecular Chaperones; Nerve Tissue Proteins; Neurons, Afferent; Preoptic Area; Rats; Rats, Wistar; Vitamin E

To assess changes of sex hormones, cortisol, prolactin (PRL) and beta-endorphins in an exhaustive aerobic performance, blood samples were taken in 11 endurance trained runners (R) along an ultra-marathon race of 110 km (T1 before the start, T2 at km 33, T3 at km 75 and T4 immediately after completing the race). Results were compared to a control group (C) who followed the race. Cortisol (p < 0.001) and beta-endorphins (p = 0.009) showed a significant increase during the race without significant modification after T2. Testosterone decreased along the race (p = 0.02). Luteinising hormone (LH) was lower at the end of the race as compared to the start in the R. No modification of PRL was noticed in the runners. Most of the modifications except for testosterone were observed from the start to T2, even in exhaustive performance no further modification was noticed from that point onwards.

Topics: Adult; Analysis of Variance; beta-Endorphin; Body Weight; Gonadal Steroid Hormones; Humans; Hydrocortisone; Luteinizing Hormone; Male; Physical Endurance; Prolactin; Running; Serum Albumin; Testosterone

The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(1) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.

Topics: Adrenocorticotropic Hormone; Animals; Arousal; Behavior, Animal; beta-Endorphin; Body Weight; Callithrix; Corticotropin-Releasing Hormone; Dexamethasone; Feedback; Female; Glucocorticoids; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Sexual Behavior, Animal; Social Behavior; Social Dominance; Stress, Psychological

A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.

Topics: Animals; beta-Endorphin; Body Weight; Corticosterone; Infusions, Intravenous; Interleukin 1 Receptor Antagonist Protein; Laminectomy; Lymphocyte Activation; Male; Organ Size; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1; Sialoglycoproteins; Spinal Cord Injuries; Temperature

This study was undertaken to investigate the effects of melanocortins and opioids on rat early postnatal body and organ growth. Among melanocortins tested desacetyl-alpha-melanocyte-stimulating hormone (alpha-MSH) at dosages of 0.3 and 3 micrograms/g/day was effective in stimulating neonatal growth with a weight gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight rise of 4.2 and 3% was obtained with 3 micrograms/g/day of both alpha-MSH and Nle4-D-Phe7 alpha-MSH. As far as opioids were concerned, while N-acetyl-beta-endorphin (beta-End) was ineffective, the activity of beta-End was dependent on dosage. Indeed, newborns treated with 0.03 microgram/g/day showed a slight, but significant, increase in weight, whereas a marked decrease in growth followed treatment with 0.3 and, mainly, 3 micrograms/g/day, with a final weight loss of 3.4 and 5.5%, respectively. All melanocortins exerted a positive action on muscular and brain trophism and, in addition, desacetyl-alpha-MSH also induced a rise of fat deposits. On the contrary, while the 0.03 microgram/g/day beta-End dose caused an increase in muscular and brain weight, the higher dosages of the opioid were detrimental, not only for muscle and brain, but also for both liver and spleen weight. A slight, although significant (P < 0.05), enhancement of serum dehydroepiandrosterone sulfate (DHEAS) level was found after the injection of 0.3 microgram/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 micrograms/g doses of desacetyl-alpha-MSH and the 3 micrograms/g dose of alpha-MSH determined the rise of plasma androstenedione (P < 0.05). All tested melanocortins and opioids failed to modify the concentrations of corticosterone. Our results suggest that melanocortins and opioids can modulate early postnatal growth in rats either by direct or indirect mechanisms.

Topics: Adipose Tissue; alpha-MSH; Animals; beta-Endorphin; Body Weight; Brain; Dose-Response Relationship, Drug; Growth; Liver; Muscle, Skeletal; Organ Size; Rats; Spleen; Weight Gain; Weight Loss

To determine whether beta-endorphin is involved in the laryngeal chemoreflex, we initially injected 0.01-1 mg of beta-endorphin into the cisterna magna (i.c.m.) and registered the respiratory and cardiovascular patterns in 5-10-d-old piglets. From 0.1 to 1 mg of beta-endorphin i.c.m. induced a decrease in the minute volume, heart rate, and blood pressure within 15 min. Within the next 30 min respiratory pauses accompanied by blood pressure increases and reductions in heart rate developed, similar to the respiratory and cardiovascular pattern of the induced laryngeal chemoreflex. Based on these initial data, we decided to induce a laryngeal chemoreflex in piglets pretreated with 0.1 mg of beta-endorphin i.c.m (n = 6), 0.2 mg of beta-endorphin i.c.m. (n = 6), 0.1 mg of beta-endorphin i.c.m. and 100 micrograms/kg naloxone i.v. (n = 6), 100 micrograms/kg naloxone i.v. (n = 6), or water i.c.m. (n = 6). Because elevated levels of hypoxanthine in the vitreous humor may indicate hypoxia before death, we therefore measured the postmortem hypoxanthine levels in the vitreous humor. The laryngeal chemoreflex-induced apnea was shortened in the piglet group pretreated with water i.c.m and naloxone i.v. (p < 0.01) and in the piglet group pretreated with 0.1 mg of beta-endorphin i.c.m and naloxone i.v. (p < 0.05), but not significantly prolonged in the piglet groups pretreated with 0.1 or 0.2 mg of beta-endorphin i.c.m. when compared with the piglets pretreated with water i.c.m.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Apnea; beta-Endorphin; Blood Glucose; Body Weight; Cisterna Magna; Female; Hematocrit; Hemoglobins; Hypoxanthine; Hypoxanthines; Injections; Larynx; Male; Pilot Projects; Reflex; Swine; Vitreous Body

The combination of prenatal ethanol exposure and footshock stress was investigated for its effects on brain beta-endorphin levels. Subjects were offspring of rats that received 1 of 3 prenatal dietary treatments: an ethanol-containing liquid diet, a identical liquid diet with ethanol substituted isocalorically with maltose-dextrin (pair-fed group), and standard laboratory rat chow (chow-fed group). Two different stress paradigms were used: a short (30-sec) footshock stress paradigm and a prolonged (180-sec) footshock stress paradigm. Levels of beta-endorphin were measured with radioimmunoassay in eight brain regions of unstressed (baseline) rats, and of stressed rats at 3 and 30 min following termination of the stress. Seven brain regions containing high densities of beta-endorphin axons and terminals were chosen, as well as the arcuate region of the hypothalamus, the only brain region where both beta-endorphin perikarya and terminals are located. Following the short footshock stress paradigm, there were no changes in beta-endorphin levels, except for a trend toward increased levels in the pair-fed group. After the prolonged stress paradigm, levels of beta-endorphin in both the pair-fed and chow-fed groups tended to be decreased in several brain regions, including the arcuate region, at 3 min after termination of the stress. In contrast, for the prenatally ethanol-exposed group, beta-endorphin levels were increased significantly in the arcuate region, and moderately increased in the septal/preoptic region and medulla/pons at 3 min after the prolonged stress paradigm.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alcohol Drinking; Animals; Axons; beta-Endorphin; Body Weight; Brain; Brain Mapping; Electroshock; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Male; Rats; Rats, Sprague-Dawley; Stress, Psychological

The pro-opiomelanocortin-derived peptides beta-endorphin (beta-EP) and alpha-melanocortin (alpha-MSH) were administered to normal and dystrophic C57BL6J mice. All groups of normal and dystrophic mice which had been treated with the two peptides gained significant body weight, as did the normal and dystrophic saline-treated male controls, but the normal and dystrophic female controls did not. The plasma activity of creatine phosphokinase (CPK) was lower in normal mice and dystrophic males which had been treated with the two peptides compared to the corresponding controls. There was no significant difference between the plasma LDH activity in any of the peptide-treated and the corresponding control groups. The activity of CPK was significantly higher in the extensor digitorum longus (EDL) muscles, but not the soleus muscles, of the peptide-treated dystrophic mice compared to the corresponding controls. Administration of alpha-MSH alone or beta-EP alone had no significant effect on the body weight or plasma CPK activity of dystrophic mice compared to the controls. However the activity of CPK was significantly higher in the EDL muscles of the alpha-MSH-treated mice than in the corresponding controls. It is possible that beta-EP and alpha-MSH act synergistically on the neuromuscular system to protect the muscles from damage.

Topics: alpha-MSH; Animals; beta-Endorphin; Body Weight; Creatine Kinase; Female; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Muscular Dystrophy, Animal; Neuromuscular Agents; Organ Size

The objective of the present studies was to investigate the effect of voluntary ethanol consumption for 21 days on the brain beta-endorphin system of C57BL/6 (alcohol-preferring) and DBA/2 (alcohol-avoiding) strains of mice. As expected, C57BL/6 mice consumed a significantly higher quantity of the 10% ethanol solution than the DBA/2 mice. Under basal conditions the content of beta-endorphin like peptides differed only in the nucleus accumbens, higher levels being found in the DBA/2 mice. Voluntary ethanol consumption induced an increase in the hypothalamic content of mRNA coding for proopiomelanocortin, associated with a significant increase in the tissue content of beta-endorphin-like peptides in the arcuate nucleus and septum of the C57BL/6 mice, but did not alter the activity of the brain beta-endorphin system of the DBA/2 mice. Since voluntary ethanol consumption was not associated with nutritional deficits and stress, the ethanol-induced enhanced activity of the brain beta-endorphin system of the C57BL/6 mice must be a direct effect of ethanol and may be important in controlling the voluntary ethanol consumption by this strain of mice.

Topics: Alcohol Drinking; Analysis of Variance; Animals; beta-Endorphin; Body Weight; Brain; Choice Behavior; Disease Models, Animal; Ethanol; Male; Mice; Mice, Inbred C57BL; Pro-Opiomelanocortin; Radioimmunoassay; RNA, Messenger

The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; beta-Endorphin; Blood Urea Nitrogen; Body Weight; Dextroamphetamine; Dopamine; Edema; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Humans; Hypotension, Orthostatic; Middle Aged; Renin; Sodium; Spironolactone; Syndrome; Vasopressins

Endogenous opioid peptides have been hypothesised to play a regulatory role in exogenous opiate agonist dependence. It was hypothesised that exercised rats would demonstrate increased beta-endorphin (beta EP) levels and decreased exogenous opiate intake. After providing morphine or methadone as their sole liquid, drug preference levels were determined by amounts of exogenous opiate consumed when rats were offered a choice between drugged and nondrugged solutions. Treatment animals were exercised in a treadmill and were found to consume significantly less exogenous opiate than control animals. Plasma, pituitary, and whole brain beta EP levels were nonsignificantly higher in exercised animals. Differences were observed in the drug ingestion patterns of morphine- and methadone-exposed rats.

Topics: Administration, Oral; Animals; beta-Endorphin; Body Weight; Brain Chemistry; Drinking; Male; Methadone; Morphine; Physical Exertion; Rats

Dissociation is made manifest by a failure to integrate thoughts, feelings, memories, and actions into a unified sense of consciousness. Although dissociation is presumed to be a special state of consciousness manifested by state-dependent memory and physiology, the psychobiology of dissociation is poorly understood. In this study, we examined cerebrospinal fluid levels of the major monoamine metabolites and beta-endorphin in patients with eating disorders (11 with anorexia nervosa, 16 with bulimia nervosa), while they were acutely ill. Dissociative capacity was measured using the Dissociative Experiences Scale (DES). We provide evidence that neurochemical changes in dopaminergic, serotonergic, and opioid systems may be associated with the clinical expression of dissociation in patients with eating disorders during the acute phase of their illness. These preliminary results are compatible with previous studies of neurochemical disturbances in the eating disorders and suggest that future work in dissociation should specifically include examination of these neurobiologic systems.

Topics: Adolescent; Adult; Anorexia Nervosa; beta-Endorphin; Body Weight; Brain; Bulimia; Dissociative Disorders; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Hypnosis; Mental Recall; Methoxyhydroxyphenylglycol; Neurotransmitter Agents; Pilot Projects; Synaptic Transmission

The exact nature of the interaction between energy balance and reproduction is still elusive. Theoretically, nutrition-related variables must reach the hypothalamic luteinizing-hormone-releasing hormone (LHRH) network and/or its neuronal inputs, to alter plasma luteinizing hormone (LH) and therefore reproductive activity. In an attempt to assess the potential mechanism of such interaction at the median eminence (ME) level, the area of hypophysiotropic LHRH neuronal terminals and release, we used a decreased caloric intake lamb model which delays the onset of puberty. Thus, we determined the in vivo release of neuropeptides, by push-pull cannula (PPC) sampling from the posterior-lateral ME, in feed-restricted (FR) ewe lambs and in full-fed (FF), age-matched, contemporary control animals. Specifically, we assessed: (1) serum LH and ME in vivo release of LHRH, beta-endorphin (beta-END) and neuropeptide Y (NPY); beta-END and NPY are two putative neuronal inputs to LHRH neuronal terminals at the ME, reported to be involved in the control of both reproduction and feed intake; (2) the effect that exogenous infusion of beta-END through the PPC might have on the release of ME LHRH and NPY, and on plasma LH. In contrast to other works, the present results were obtained in lambs with intact ovaries. Furthermore, FR lambs were always compared statistically with FF contemporary paired controls that had attained puberty. Feed restriction decreased ME LHRH release, lowered plasma LH and prevented the onset of puberty. The changes induced by feed restriction in both LHRH and LH release were associated predominantly with decreases in pulse amplitude, rather than alterations in pulse frequency. The decreased LHRH and LH release occurred in the presence of a decreased beta-END but unchanged NPY release from the ME. Exogenous infusion of beta-END into the posterior-lateral ME decreased both LHRH and NPY release from this site and decreased plasma LH. In conclusion, decreased caloric intake lowers LH release and prevents puberty onset by decreasing the amplitude of the LHRH output from the hypothalamic hypophysiotropic network. A compensatory but unsuccessful mechanism for the FR status might be a lower beta-END-inhibitory tone on ME LHRH neuronal terminals. The unchanged release of NPY at this site supports the specificity of the changes induced by feed restriction on LHRH and beta-END in vivo release.

Topics: Animals; beta-Endorphin; Body Weight; Diet; Eating; Energy Intake; Female; Gonadotropin-Releasing Hormone; Median Eminence; Neuropeptide Y; Progesterone; Sexual Maturation; Sheep

Feeding and its regulation by opioids were studied in lean sheep and sheep in the static phase of dietary obesity. Sheep were fasted 16 h and on separate days were injected IV with 0 (saline), 0.01, 0.1, 1, or 3 mg/kg naloxone 5 min before they were allowed ad lib intake for the ensuing 32 h. All sheep were in chronic zero energy balance when not fed ad lib during naloxone treatment. After 0 mg/kg naloxone, intake rate was at least twice as fast (p < 0.05) in lean than obese sheep through the first 4 h of ad lib feeding, but was similar (approximately 0.5 g/min) in both groups of sheep after 8 h of ad lib feeding. Dose-dependent inhibitory effects of naloxone on intake were observed in lean and obese sheep through the first 4 h of ad lib feeding with maximum inhibition at +2 h. Dose-response curve for naloxone inhibition of intake was shifted leftward in obese compared with lean sheep. Dose of naloxone needed to inhibit intake by 25% was less (p < 0.05) in obese (0.13 mg/kg) than lean (0.57 mg/kg) sheep when both groups experienced similar plasma concentrations of injected naloxone. Basal concentrations of immunoreactive beta-endorphin in fasted plasma were similar in lean (33 +/- 4 pg/ml) and obese (48 +/- 9 pg/ml) sheep. Dietary obesity in sheep was associated with reduced appetite and with enhanced responsiveness to the intake-inhibitory effects of naloxone.

Topics: Animals; Appetite; beta-Endorphin; Body Weight; Dose-Response Relationship, Drug; Endorphins; Feeding Behavior; Female; Naloxone; Receptors, Opioid; Sheep

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Corticotropin-Like Intermediate Lobe Peptide; Macaca mulatta; Peptide Fragments; Pituitary Gland; Pro-Opiomelanocortin; Protein Processing, Post-Translational

Basal and dexamethasone-suppressed adrenal glucocorticoid secretion and hypothalamic beta-endorphin (BE) release in vitro were investigated in rats deprived of food for 24, 48, 72, and 96 h. Fasting for up to 48 h neither caused significant changes in serum corticosterone levels nor in the suppressive effect of dexamethasone. Food deprivation for 72-96 h resulted in increased basal serum corticosterone, diminished suppression by dexamethasone, and a significant involution of the thymus. Basal in vitro BE release from hypothalamic explants was significantly increased after the first day of food deprivation, and in vitro perifusion with corticotropin-releasing hormone (CRH) failed to enhance BE release further. With continuing food deprivation, basal BE release remained significantly greater than that from hypothalami originating from normally fed control rats. The stimulatory effect of CRH on BE release was only partially restored after 2 days of fasting. The results suggest that food deprivation for more than 2 days increases basal glucocorticoid secretion, and signs of impairment in hypothalamic-pituitary-adrenal regulation become apparent. These findings might be implicated in the pathogenetic mechanisms of endocrine dysregulation in diseases related to caloric reduction.

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Glucose; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Dexamethasone; Food Deprivation; Hypothalamus; In Vitro Techniques; Male; Organ Size; Pituitary-Adrenal System; Rats; Rats, Wistar; Thymus Gland; Time Factors

The place of laparoscopic surgery continues to increase in the field of surgery in our specialty. Although the advantages would seem to be obvious, it seemed to us interesting to quantify, if possible, the parameters of operative stress and compare laparoscopic surgery with conventional surgery. Markers studied are Prolactin, Cortisol, Adrenaline, Nor-Adrenaline, Dopamine and the Beta-Endorphins. The only marker that shows any difference in the two procedures in our study is Beta-Endorphin which is significantly less raised in laparoscopic surgery directly after the operation (p less than 0.01). This was very specific for pain, which is one of the benefits of this technique and shown in this parameter which confirms the clinical impression. The curves of the changes in the different markers have been analysed and discussed.

Topics: Adult; beta-Endorphin; Biomarkers; Body Weight; Dopamine; Epinephrine; Evaluation Studies as Topic; Female; Humans; Hydrocortisone; Infertility, Female; Intraoperative Complications; Laparoscopy; Laparotomy; Norepinephrine; Ovarian Cysts; Prolactin; Stress, Physiological; Time Factors

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Kinetics; Male; Obesity; Reference Values

The peripheral secretion of endogenous opioids was studied in 10 women with restrictive anorexia nervosa and 10 age- and sex-matched healthy controls. The circadian rhythm of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH), and their responses to the administration of corticotropin releasing hormone (CRH, 1 micrograms/kg body weight, i.v.), clonidine (150 microgram, i.v.), domperidone (10 mg, i.v.), and 5-hydroxytryptophan (5-HTP, 200 mg, p.o.) were examined in patients and controls. The results revealed increased nocturnal secretion of beta-EP and diurnal-nocturnal secretion of beta-LPH with loss of circadian rhythmicity of both peptides, normal response to CRH stimulation, blunted response to clonidine and domperidine, and normal beta-EP and blunted beta-LPH response to 5-HTP stimulation. The data suggest a complex alteration of peripheral opioids and of central aminergic mechanisms that regulate proopiomelanocortin-derived peptide secretion and eating behavior.

Topics: 5-Hydroxytryptophan; Adolescent; Adult; Anorexia Nervosa; beta-Endorphin; beta-Lipotropin; Body Weight; Circadian Rhythm; Clonidine; Corticotropin-Releasing Hormone; Domperidone; Endorphins; Female; Humans; Receptors, Opioid; Secretory Rate

This study tested the role of melatonin in the regulation of seasonal physiological change in the pony stallion. Four 3-year-old, Welsh Mountain pony stallions were housed initially under the prevailing short-day photoperiod in December (8 of light [L]:16 h of darkness [D]) before being transferred to long days (16L:8D) on 13 January for the remaining 22 weeks of the study. On Day 76 (11 weeks later) the stallions began an 11-week period of daily melatonin treatment (20 mg orally, 8 h after lights on). Marked changes in mean plasma testosterone, beta-endorphin and cortisol concentrations occurred in response to long days and to subsequent melatonin treatment. Photostimulation produced a sharp rise in overall mean daily testosterone to a peak of 6.74 nmol/litre by Day 30. Values then fell to a nadir (3.17 nmol/litre) by Day 85, suggesting a role for melatonin in the termination of breeding activity in the horse. Cortisol and beta-endorphin values remained low throughout the first 11 weeks, but by Day 105 (Day 30 of melatonin treatment) concentrations had risen sharply, attaining a peak on Day 125 (510 pg beta-endorphin/ml, 50 ng cortisol/ml). Concentrations of both hormones had fallen by Day 77 of melatonin treatment (Day 152), perhaps as a result of refractoriness. Parallelism between beta-endorphin and cortisol suggests a pituitary origin for peripheral beta-endorphin. Diurnal variation in cortisol was observed under long days but no change in beta-endorphin was detected. Long days and melatonin treatment stimulated shedding of the winter and summer coats respectively, whereas growth rate was increased (2.03 kg/week) during the period of melatonin treatment relative to that of long days only (0.37 kg/week). The study provides evidence that the diurnal pattern of melatonin secretion mediates the reproductive and non-sexual responses to photoperiodic change in pony stallions.

Topics: Administration, Oral; Animals; beta-Endorphin; Body Weight; Circadian Rhythm; Horses; Hydrocortisone; Light; Male; Melatonin; Seasons; Testosterone

Beta-endorphin (beta-Ep) plasma levels are higher in obese patients than in normal subjects. To establish that this finding constitutes hyperendorphinemia, 28 obese patients aged 12-55 years, six males and 22 females, (weighing 61-117 kg) were investigated twice by an overnight 1-mg p.o. dose dexamethasone suppression test (DST) before and after weight loss. beta-Ep was measured by radioimmunoassay (RIA). Before body weight loss, beta-Ep was higher than normal and unresponsive to DST, whereas ACTH and cortisol were suppressible. After weight loss, beta-Ep was slightly reduced but still insensitive to DST. ACTH and cortisol were responsive as usual. Findings suggest a resistance to DST in obesity as far as beta-Ep is concerned. The disorder persists even after weight loss, indicating that hyperendorphinemia is not secondary to body weight excess. Accordingly, one can argue that the unresponsiveness of the endorphinergic system to its physiological feedback is a pathophysiological characteristic of obesity.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Weight; Dexamethasone; Feedback; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Radioimmunoassay; Weight Loss

The effects of lesions of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) of the hypothalamus on photoperiodic responses were examined in adult Siberian hamsters. SCN lesions reduced nocturnal water intake in long days, whereas PVN lesions increased body weight and food intake in both short and long days. SCN or PVN lesions blocked short-day-induced decreases in body, fat pad, and testes weights and in food intake. Serum prolactin (PRL), but not follicle-stimulating hormone, levels were increased. The distribution of immunostained neurons and fibers for gonadotropin-releasing hormone (GnRH), beta-endorphin, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) resembled that of other rodent species. Short-day exposure reduced AVP staining in lateral septum, medial amygdala, and bed nucleus of the stria terminalis but not in the PVN of the thalamus or the SCN. Short-day-exposed hamsters had fewer beta-endorphin-positive arcuate nucleus cells and tended to have fewer GnRH-positive preoptic cells than long-day controls. VIP staining was unaffected by photoperiod. Most day length effects on immunostaining were eliminated by either lesion. These results establish the importance of the SCN and PVN in the photoperiodic control of several seasonal responses in Siberian hamsters.

Topics: Analysis of Variance; Animals; Arginine Vasopressin; beta-Endorphin; Body Weight; Brain Diseases; Circadian Rhythm; Cricetinae; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Immunohistochemistry; Luteinizing Hormone; Male; Melatonin; Neuropeptides; Paraventricular Hypothalamic Nucleus; Prolactin; Suprachiasmatic Nucleus; Testis; Vasoactive Intestinal Peptide

To investigate the mechanism(s) during pubertal development by which androgens alter hypothalamic proopiomelanocortin (POMC) gene expression and beta-endorphin content, we used the technique of in situ hybridization histochemistry and the androgen-insensitive testicular feminized (Tfm) rat. We evaluated POMC mRNA levels in the arcuate nuclei and periarcuate regions of 12 coronal brain slices from prepubertal (age, 30 days) and adult (age, 60 days) normal male and Tfm rats (n = 4 for each group). Hybridizations were performed using an 35S-radiolabeled oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. The tissue sections were sequentially exposed to x-ray film and photographic emulsion with subsequent analysis by both densitometry and computer-assisted grain counting. beta-Endorphin was measured in hypothalamic tissue blocks from similar animals in each of the four experimental groups. The results of densitometry and grain counting were consistent and revealed an increase in POMC mRNA with pubertal development in both the male and Tfm animals. The concentration of hypothalamic beta-endorphin was greater for the adult Tfm animals than for all other groups, which did not differ from each other. These results suggest that androgens may stimulate POMC gene transcription by their action through estrogen receptors after conversion by aromatase. Alternatively, additional pubertal factors may be responsible for act directly through their respective receptors to alter translation, posttranslational processing, or secretion of beta-endorphin, resulting in diminished intracellular hypothalamic peptide concentration.

Topics: Animals; beta-Endorphin; Body Weight; Gene Expression Regulation; Gonadal Steroid Hormones; Histocytochemistry; Hypothalamus; Male; Nucleic Acid Hybridization; Osmolar Concentration; Pro-Opiomelanocortin; Rats; Receptors, Androgen

The responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin (0.5 mg/h) were studied in 10 formerly obese subjects who had lost 35 kg by dieting (body mass index less than 25) and compared with those of 10 normal-weight control (body mass index less than 25) and 10 obese (body mass index greater than 30) subjects. The fasting plasma concentrations of beta-endorphin were significantly higher in both the obese and the post-obese group than in the control group. In both obese and post-obese subjects, the infusion of beta-endorphin caused significant increases in peripheral plasma glucose, insulin, C-peptide and glucagon concentrations. In the control group, matched for age, sex and weight with the formerly obese group, there was no appreciable change in plasma insulin and C-peptide concentrations during the infusion of beta-endorphin, but the rise in plasma glucose was more sustained. Thus, 1. the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; and 2. formerly obese, normal-weight subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin infusion. The alteration of the opioid system in human obesity may play some role in the predisposition to weight gain.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Humans; Insulin; Kinetics; Male; Obesity

The effects of chronic alcohol administration on reproductive endocrinology in the developing male rat were examined. Prepubescent male rats (25 days of age) were maintained on an alcohol liquid diet or were pair-fed a control diet until early adulthood and selected indices of sexual maturation were examined at weekly intervals. To determine whether sexually immature animals were more sensitive to the effects of alcohol than adults, fully mature male animals were exposed to an identical period of alcohol exposure and comparisons were made between the two groups. The results demonstrated that alcohol significantly affected many of the primary indices of puberty and sexual maturation. The normal pubertal increases in serum testosterone levels, the weights of the testes and secondary sex organs and beta-endorphin levels in the hypothalamus were substantially reduced in alcohol-exposed animals compared with controls. In contrast to these results, the effects of alcohol on reproductive endocrinology in the fully mature animal were transitory and of considerably less magnitude. After a 2-week alcohol-free period, male rats exposed to alcohol during development were bred with drug-naive primiparous females. Although the same number of pregnancies resulted from matings between alcohol-exposed males and drug-naive females compared with controls, litter sizes were significantly smaller in alcohol-derived offspring than in controls. In all other respects, such as body weights, sex ratios, mortality rates and gross developmental features (eye opening, incisor eruption and testes descent), alcohol-derived offspring were identical with controls. Upon closer examination, however, significant disturbances were detected in alcohol-derived male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta-Endorphin; Body Weight; Ethanol; Female; Fetus; Hypothalamus; Luteinizing Hormone; Male; Organ Size; Pregnancy; Rats; Rats, Inbred Strains; Reproduction; Seminal Vesicles; Sexual Maturation; Spermatozoa; Testis; Testosterone

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.

Topics: Adolescent; Adult; beta-Endorphin; Blood Urea Nitrogen; Body Weight; Cholesterol; Creatinine; Fasting; Female; Homeostasis; Humans; Hydrocortisone; Male; Uric Acid

1. Immunoreactive (IR)-met-enkephalin and beta-endorphin contents in the hypothalamus and the pituitary were measured in alloxan-diabetic rats with or without insulin treatment. 2. Both IR-met-enkephalin and IR-beta-endorphin in the pituitary were substantially reduced in alloxan-diabetic rats 1 month after treatment. 3. Hypothalamic IR-beta-endorphin content was also significantly lower. 4. Gel-filtration chromatography showed that the peaks co-eluting with met-enkephalin precursor, met-enkephalin and beta-endorphin were lower in the pituitaries from the diabetic rats, whereas the peaks co-eluting with beta-endorphin precursor and beta-lipotropin were not. 5. In another experiment, the IR-beta-endorphin contents of the neuro-intermediate lobe and hypothalamus, but not the anterior lobe were significantly lowered in diabetic rats, whereas IR-met-enkephalin contents were significantly reduced in both the anterior and neuro-intermediate lobe. 6. All these changes were reversed by insulin treatment. 7. As a decrease in general protein synthesis could not explain the recorded changes, these results suggest a possible direct role of insulin in regulating the opioid peptide content of the hypothalamus and pituitary.

Topics: Animals; beta-Endorphin; Body Weight; Chromatography, Gel; Diabetes Mellitus, Experimental; Enkephalin, Methionine; Hypothalamus; Insulin; Male; Organ Size; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains

Numerous studies have shown a rise of blood sugar concentrations and serum levels of pancreatic polypeptides after pharmacological doses of beta-endorphin. We tested the yet unknown influence of physiological fluctuations in beta-endorphin serum levels on glucose homeostasis by stimulating the pituitary secretion with CRF. 100 micrograms of human CRF or saline solution were intravenously injected in ten healthy male subjects at least one week apart. beta-endorphin serum levels rose significantly after the injection of CRF, but there was no change in blood sugar concentrations or serum levels of glucagon or insulin at all. We conclude that only a pharmacological dose of beta-endorphin influences glucose homeostasis.

Topics: beta-Endorphin; Blood Glucose; Body Weight; Corticotropin-Releasing Hormone; Glucagon; Humans; Insulin; Islets of Langerhans; Male

The opioid polypeptide beta-endorphin is present in fetal blood but it is not clear whether its source is the fetus or the placenta. We therefore measured beta-endorphin in extracts of fetal femoral arterial and umbilical venous blood plasma in sheep by radioimmunoassay to determine whether the fetus or the placenta is the major source of beta-endorphin in the fetal circulation. Chromatographic analysis of extracts of fetal arterial plasma showed that beta-lipotropin and other precursors of beta-endorphin made only a minor contribution to the immunoreactivity detected. Concentrations of immunoreactive beta-endorphin were higher in the femoral artery than in the umbilical vein in fetal sheep between 113 and 128 days of pregnancy. Therefore the placenta removes beta-endorphin or a closely related polypeptide of fetal origin from the umbilical circulation in sheep at this stage of gestation. Acute hypoxaemia and hypoglycaemia increase the concentrations of immunoassayable beta-endorphin in blood plasma of adult and fetal sheep, but little is known about the effects of chronic hypoxaemia or hypoglycaemia on the circulating levels of beta-endorphin and related polypeptides in the fetus. Therefore we also measured immunoreactive beta-endorphin in blood plasma from fetal sheep in which growth retardation in association with restricted placental growth was produced by removal of endometrial caruncles before mating. Intra-uterine growth retardation was accompanied by chronic hypoglycaemia and chronic hypoxaemia in the fetuses. This was not associated with higher concentrations of beta-endorphin-like immunoreactivity in fetal arterial or umbilical venous plasma, but was accompanied by significantly increased placental extraction of fetal immunoreactive beta-endorphin from the umbilical circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta-Endorphin; Body Weight; Chromatography, Gel; Female; Femoral Artery; Fetal Blood; Fetal Growth Retardation; Organ Size; Placenta; Pregnancy; Pregnancy, Animal; Radioimmunoassay; Sheep; Umbilical Veins

Increased responses of plasma insulin and endorphins to the oral glucose tolerance test (oGTT) have earlier been found in obese women. We studied responses of immunoreactive beta-endorphin (ir beta-E) and insulin in plasma to the oGTT in 8 non-obese women with polycystic ovaries (PCO) and in 10 healthy women. An additional control group consisted of 5 healthy women who were fasting during the study period. In the PCO group the insulin and glucose responses to the oGTT were increased, and an increase of ir beta-E from 5.9 +/- 1.5 to 8.6 +/- 2.8 pmol/l was found during the 1st half-hour period of the oGTT. In contrast, no significant change was found during the oGTT in healthy women (3.2 +/- 0.5 and 2.7 +/- 0.65 pmol/l, respectively), and in the fasting control women the mean ir beta-E level (+/- SE) decreased, from 4.5 +/- 1.2 to 3.6 +/- 1.1 pmol/l. These findings revealed increased responses of both plasma ir beta-E and insulin to the oGTT in non-obese women with PCO but their possible causal relationship remained unsolved.

Topics: Adult; beta-Endorphin; Body Weight; Female; Glucose Tolerance Test; Humans; Insulin; Polycystic Ovary Syndrome

A role for beta-EP in the regulation of food intake has been suggested as a contributory factor in the obesity of some genetically obese animal models. Studies undertaken to determine whether continuous administration of beta-EP could alter food intake in normal rats are described. The present studies demonstrated that continuous subcutaneous infusion with beta-EP was ineffective in modulating food intake, but that acute intraperitoneal or intracerebroventricular administration stimulated food intake in previously food deprived or satiated animals, respectively. These results suggest that beta-EP is not involved in the long-term regulation of food intake, but under certain conditions it may play some role in the regulation of individual meals. It is speculated that the latter activity may result from the action of other appetitive regulatory hormones.

Topics: Animals; beta-Endorphin; Body Weight; Cerebral Ventricles; Eating; Infusion Pumps, Implantable; Infusions, Parenteral; Male; Rats; Rats, Inbred Strains; Sincalide

1. To examine individual hormonal responses to extreme physical stress, blood samples were taken from eight highly trained athletes 1 day before and within 15 min of finishing the 1986 1000 km Sydney to Melbourne Ultramarathon foot race. 2. The baseline hormonal state of these highly trained athletes was quite different from normal. Resting serum conjugated catecholamines--epinephrine (E), norepinephrine (NE), dopamine (D), free E and free D--were significantly elevated above the normal mean (P less than 0.01). ACTH levels were significantly elevated above the normal range. Immunoreactive beta-endorphin (IR-beta EP), growth hormone (GH), prolactin (PRL), testosterone, cortisol and cortisol-binding globulin (CBG) were within the normal range. 3. The effect of the race on serum catecholamine levels was to elevate further free and conjugated NE (P less than 0.01). Other catecholamines, free and conjugated, remained significantly elevated above the normal mean (P less than 0.01). Adrenocorticotrophic hormone (ACTH) remained elevated, and IR-beta EP within the normal range, without significant change. A significant increase in GH (P less than 0.05), PRL (P less than 0.01), and cortisol (P less than 0.01) was seen, with no change in CBG. 4. As a model of chronic physical stress, the ultramarathon runner demonstrates a significantly altered baseline hormonal state as reflected in the primary mediators of the stress response, the catecholamines and the hypothalamic-pituitary-adrenal axis. Their response to severe exercise is distinct from that of untrained individuals in whom conjugated catecholamines decrease and ACTH increase. This may represent hormonal adaptation to prolonged stress.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Body Height; Body Weight; Catecholamines; Fats; Female; Growth Hormone; Humans; Hydrocortisone; Hyponatremia; Male; Prolactin; Running; Testosterone

To determine whether prenatal exposure to ethanol alters the response of the beta-endorphin (beta-EP) system to stress, the effect of two types of stressful stimuli, ether and cold, was examined in the offspring of rats which during pregnancy were: (a) fed with an ethanol-containing diet; (b) pair-fed with an isocaloric sucrose diet; and (c) fed ad libitum with standard lab chow (basic control group). The effect of stress on the content of beta-EP in the serum, pituitary gland and hypothalamus, as well as on the serum corticosterone and hypothalamic corticotropin-releasing factor (CRF) content was examined. Pups prenatally exposed to ethanol had significantly higher serum beta-EP levels on Day 1 and higher serum corticosterone levels on Days 1-3 when compared to their pair-fed or basic controls. On all days tested pituitary beta-EP content was lower in the offspring of the ethanol-treated rats than in the control groups. There was no difference in the total hypothalamic beta-EP content between the three treatment groups; however, during the first 10 days of life a higher concentration (ng/mg protein) of beta-EP was observed in the hypothalami of the ethanol and the pair-fed group when compared to the basic control pups. Hypothalamic CRF levels, though significantly lower in the pups exposed to ethanol in utero than in the control groups on Day 3, increased significantly in the ethanol group between Days 14 and 22, while no significant change was observed during this period in either of the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arousal; beta-Endorphin; Body Weight; Brain; Corticosterone; Female; Fetal Alcohol Spectrum Disorders; Hypothalamo-Hypophyseal System; Organ Size; Pituitary-Adrenal System; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Opioid; Stress, Psychological

We have recently demonstrated that the pineal neurohormone melatonin can enhance immune reactivity in normal mice and counteract the effects of acute stress or corticosterone treatment on antibody production, thymus weight and anti-viral resistance. These remarkable immunopharmacologic effects of melatonin were abolished by naltrexone, suggesting an involvement of the endogenous opioid system. Here we compared the immunopharmacologic action of beta-endorphin, dynorphin 1-13, leu-enkephalin and metenkephalin with that of melatonin in restraint-stressed or prednisolone-treated mice and in normal nonstressed animals. We found that beta-endorphin and dynorphin 1-13 can mimic the immunoenhancing and antistress effect of melatonin. However, at variance with the pineal neurohormone, these opioids were effective in umprimed mcie, too. We found also that restraint stress or prednisolone treatment decreases the immunopharmacologic potency of beta-endorphin and augments that of dynorphin 1-13. In fact, at the doses used, beta-endorphin enhanced the antibody response in normal but not in stressed or prednisolone-treated mice, while dynorphin 1-13 was effective only in counteracting the effect of stress or prednisolone treatment. Most interestingly, all these effects proved to be dependent on the time of administration, i.e. showed a circadian rhythm in analogy with the effects of melatonin. Again, naltrexone abolished all the opioid effects, indicating that their action was exerted via opioid receptors. These findings have important scientific and practical implications.

Topics: Adjuvants, Immunologic; Animals; beta-Endorphin; Body Weight; Circadian Rhythm; Dynorphins; Erythrocytes; Female; Hemolytic Plaque Technique; Melatonin; Mice; Mice, Inbred BALB C; Naltrexone; Organ Size; Prednisolone; Restraint, Physical; Stress, Psychological; Thymus Gland

1. The effects of 72 h subcutaneous infusion of graded doses of rat CRF and ACTH(1-24) were studied in rats of initial weight 150-170 g. Rat CRF was infused at 30, 100 or 300 ng/h, and ACTH(1-24) at 125, 250 or 500 ng/h. 2. There was a progressive though modest increase in adrenal weight for all CRF doses, and an associated reduction of thymus weight. Circulating ir-ACTH, ir-beta-endorphin and corticosterone levels, and adrenal DNA content, were not increased after 3 days. Adrenal RNA and protein content were increased at the highest CRF dose used. 3. ACTH infusion caused a progressive increase in adrenal weight and thymic involution which was marked at the higher doses; circulating corticosterone levels were not significantly altered by the lowest dose but were significantly raised by the higher doses. As expected, plasma ir-beta-endorphin was suppressed to low levels with all doses. Adrenal DNA did not alter but there were progressive increases in adrenal protein and RNA. 4. There was a marked difference in gain between the two infusion regimens in terms of all parameters measured, suggesting that potent mechanisms exist to temper the pituitary-adrenal response to markedly different levels of peripheral CRF input. The damped effect of CRF infusion compared with that of ACTH may represent desensitization of CRF receptors at the pituitary; alternatively, it may reflect binding and substantial inactivation of CRF in peripheral blood.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; DNA; Injections, Subcutaneous; Male; Organ Size; Peptides; Pituitary-Adrenal System; Proteins; Radioimmunoassay; Rats; Rats, Inbred Strains; RNA; Thymus Gland

Two weeks following a single exposure to either soman (100 micrograms/kg, sc) or saline, rats were sacrificed at 2-hr intervals over a 26-hr period. Trunk blood was collected and plasma was stored until assayed for corticosterone, prolactin, growth hormone, adrenocorticotropin, beta-endorphin, and beta-lipotropin. Rats surviving for 2 weeks following soman appeared well groomed and were gaining weight at a rate similar to saline-treated rats at the time of termination. Thus, they appeared to have recovered from the initial physiological effects of soman exposure. However, substantial differences in plasma levels of most hormones were seen in comparing soman- vs saline-treated rats. Levels of prolactin were suppressed at all time points in soman-treated rats. Growth hormone secretion was also suppressed and the normal episodic peaks of growth hormone were missing in soman-treated rats. Both soman- and saline-treated rats displayed circadian rhythms in levels of plasma corticosterone, but the usual late afternoon rise in plasma corticosterone levels was shifted to earlier time points in the soman-treated rats. Levels of beta-endorphin and beta-LPH were slightly but significantly suppressed in soman-treated rats at almost all time points. Levels of adrenocorticotropin were similar in control and soman-treated rats. The results of this experiment demonstrate that a single exposure to soman may have long-lasting effects on neuroendocrine function.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Temperature; Body Weight; Brain; Corticosterone; Growth Hormone; Hormones; Male; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Soman; Time Factors

B-Endorphin (B-Ep), ACTH and cortisol circulating levels, before and after a two months therapy with a hypocaloric diet and an increase in physical exercise, were measured by RIA in 17 obese female subjects. After therapy, the body weight excess fell from 56.6 +/- 22.2% to 38.6 +/- 22.1% (p less than 0.01). Plasma levels of B-Ep decreased from 18.3 +/- 12.5 fmol/ml to 6.4 +/- 3.5 fmol/ml (p less than 0.01); those of ACTH from 46.8 +/- 22.8 pg/ml to 31.2 +/- 11.6 pg/ml (p less than 0.01); and those of cortisol from 15.9 +/- 4.6 micrograms% to 10.3 +/- 2.5 micrograms% (p less than 0.01). The reduction of the elevated plasma B-Ep levels found in obese subjects is related principally to the diet therapy. Thus, as shown in experimental animals, excessive feeding results in an increased hypothalamic-pituitary secretion of B-Ep.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Weight; Diet, Reducing; Energy Intake; Female; Humans; Hydrocortisone; Obesity; Physical Exertion

Topics: Animals; beta-Endorphin; Body Weight; gamma-Aminobutyric Acid; Insulin; Obesity; Rats; Rats, Zucker; Valproic Acid

Rats which received a liquid diet containing 6.5% (w/v) ethanol for three weeks became tolerant to the hypothermic effect of an acute dose of ethanol. Withdrawal of this diet was followed by loss of the tolerance within 3 days, and by an accompanying pattern of changes in levels of immunoreactive-ir-beta-endorphin in several brain regions. An initial decrease in levels on days 1 and 3 of withdrawal was followed by recovery to control levels on days 8 and 15. This pattern was found in the arcuate nucleus, amygdala, septum, periventricular thalamus and pre-optic periventricular hypothalamus (POPH), but was statistically significant only in the POPH. A different pattern of change in ir-beta-endorphin levels was found in the pituitary. The anterior lobe showed a significant depletion of ir-beta-endorphin levels before alcohol withdrawal, which recovered by day 8 of withdrawal. This depletion was probably not related to the loss of tolerance to ethanol but was a response to a perturbation of the hypothalamic-pituitary axis of hormonal control.

Topics: Animals; beta-Endorphin; Body Temperature; Body Weight; Brain; Ethanol; Male; Organ Specificity; Pituitary Gland; Rats; Rats, Inbred Strains; Reference Values; Substance Withdrawal Syndrome

The discovery that the endogenous opioid peptides contribute to the modulation of appetitive behavior and neuroendocrine function has raised questions as to whether disturbances of opioids contributes to the pathophysiology of eating disorders. To assess central nervous system (CNS) beta-endorphin in patients with anorexia nervosa we measured cerebrospinal fluid (CSF) beta-endorphin concentrations before, and at intervals after weight correction. In addition, we measured three sister peptides (beta-lipotropin, adrenocorticotropic hormone (ACTH), and the N-terminal fragment) derived from the same precursor molecule, pro-opiomelanocortin (POMC) to determine whether possible disturbances might extend to sister peptides. Underweight anorectics (58 +/- 5% of average body weight (ABW), n = 10) had significantly lower CSF concentrations of all 4 peptides compared to healthy controls (102 +/- 10% ABW, n = 11). CSF concentrations of all 4 POMC-related peptides were found to be significantly increased when the same anorectics were restudied 4 to 6 weeks after weight gain (83 +/- 4% ABW). After weight gain, levels of CSF beta-endorphin, beta-lipotropin, and ACTH were similar to controls, whereas levels of CSF N-POMC remained significantly less than controls. Another group of women, previously underweight with anorexia nervosa, but weight-restored (93 +/- 11% ABW, n = 12) for greater than 1 year had CSF concentrations of all 4 POMC-related peptides that were similar to controls. We conclude that underweight anorectics have state-associated disturbances of CNS beta-endorphin as well as other POMC-related peptides. These abnormalities are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic alterations in behavior and neuroendocrine function.

Topics: Adrenocorticotropic Hormone; Adult; Anorexia Nervosa; beta-Endorphin; beta-Lipotropin; Body Weight; Female; Humans; Peptide Fragments; Pro-Opiomelanocortin

In Zucker obese rats (fa/fa) there are disturbances in the regulation of ACTH and corticosterone. In addition, beta-endorphin concentrations are higher in the pituitary and hypothalamus in obese than in lean rats. Since ACTH and beta-endorphin are thought to be controlled by corticotropin releasing factor (CRF), these effects may be due to abnormalities in CRF regulation. This possibility was investigated by immunizing rats against CRF. Obese rats immunized against CRF developed higher titer antibodies than lean rats. Hypothalamic CRF concentrations were higher in CRF-immunized obese but not lean rats compared with those of control rats, suggesting that compensation for sequestration of peripheral CRF developed in obese rats. In obese, but not lean rats, immunization against CRF decreased weight gains during weeks 1-4 and increased gains during weeks 9-12 and food intakes were decreased during weeks 5-8 compared with those for obese rats immunized against bovine serum albumin (BSA). Adrenal glands weighed 30% less in both obese and lean rats immunized against CRF compared with those immunized against BSA. These responses to immunization against CRF occurred even though plasma, hypothalamic and pituitary concentrations of ACTH and beta-endorphin were unaffected at the end of the study.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Eating; Female; Hypothalamus; Immunization; Insulin; Rats; Rats, Zucker

Administration of gonadal steroids to neonatal rats has a profound effect on the function of the neuroendocrine system in the adult animal. Considering that gonadal steroids modulate hypothalamic and pituitary levels of beta-endorphin (BE) in adult male and female rats, the effects of neonatal gonadal steroid treatment on BE levels in the adult animal were investigated. Neonatal male rats were administered testosterone and neonatal female rats were treated with estrogen. Matched control littermates received vehicle. All animals were sacrificed at 90 days of age. Neonatal gonadal steroid treatment did not affect the level of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) of male rats but did result in a significant increase in IR-BE in the AP of female rats. Neonatal administration of gonadal steroids produced a significant decrease in IR-BE in the neurointermediate lobe of the pituitary (NIL) of both male and female rats, with the magnitude of the decrease being greater in the NIL of the female rats. IR-BE levels in the hypothalamus of male or female rats were not altered by the treatments. Column chromatography indicated that the increase in IR-BE in the AP represented a proportional increase in BE and beta-lipotropin, while the reduction in IR-BE in the NIL of the treated rats represented a reduction in BE. These findings suggest that gonadal steroids may influence the development of the neurotransmitter systems which regulate BE levels in the adult pituitary, the development of the biosynthetic mechanisms of the adult pituitary, or both.

Topics: Animals; Animals, Newborn; beta-Endorphin; Body Weight; Endorphins; Estrogens; Female; Gonadal Steroid Hormones; Hypothalamus; Male; Pituitary Gland; Rats; Rats, Inbred Strains; Testosterone

Pregnant rats were fed an ethanol diet from the first day of pregnancy until parturition. Control rats were either pair fed with an isocaloric sucrose diet, or fed with standard lab chow (basic control group). Rats fed with the ethanol diet and their pair-fed controls showed a similar increase in body weight during pregnancy, which was lower than the increase observed in the basic control group. At 10 days after ethanol withdrawal all three groups presented similar body weights. A lower body growth was exhibited by the offspring of both the ethanol and the sucrose pair-fed rats, implicating a prenatal nutritional factor on the postnatal growth. Furthermore, the rate of body growth was lower in the offspring of the ethanol-treated animals than in the offspring of both their pair-fed and the basic control rats, indicating the presence of an additional ethanol-associated factor. On day 4 of development, the concentration of beta-endorphin peptides (pmol/mg protein) in the pituitary gland and the anterior lobe, of the offspring of the ethanol-treated animals and their sucrose pair-fed controls, was significantly higher than that of the offspring of the basic control animals. However, a lower content of beta-endorphin-like peptides was noticed in the whole pituitary gland, the anterior lobe, and the intermediate lobe of the offspring of the ethanol-treated rats and their pair-fed controls on days 8, 14, and 22 postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta-Endorphin; Body Weight; Ethanol; Female; Growth; Pituitary Gland; Pituitary Gland, Anterior; Pregnancy; Rats; Rats, Inbred Strains; Sucrose

Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta-endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin-(PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta-receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa-receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu-agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U-50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as "hyperalgesic": of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis, Experimental; beta-Endorphin; Body Temperature; Body Weight; Endorphins; Feeding Behavior; Male; Morphine; Narcotic Antagonists; Pain; Prolactin; Pyrrolidines; Rats; Receptors, Opioid

The hyperphagia and obesity induced by ventromedial hypothalamic (VMH) electrolytic lesions in female rats were associated with a 70-94% decrease in the level of beta-endorphin (beta-E) in the hypothalamus and other regions of brain, but not in the pituitary. Dynorphin (Dyn) and methionine-enkephalin (ME) levels were also decreased. Rats with VMH lesions were less sensitive to the inhibitory effect of naloxone on their food-intake. Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress.

Topics: Analgesia; Animals; beta-Endorphin; Body Weight; Brain; Dynorphins; Enkephalin, Methionine; Feeding Behavior; Female; Pituitary Gland; Rats; Rats, Inbred Strains; Ventromedial Hypothalamic Nucleus

When rats were tested more than two weeks following surgery, lesions of the medial basal hypothalamus centered on the arcuate nucleus enhanced a form of foot-shock stress-induced analgesia (SIA) that was not blocked by injections of the opiate receptor blocker, naltrexone (6 mg/kg;). These arcuate nucleus lesions reduced the SIA produced by the same stressor when similar rats were tested 3-4 days following surgery. Finally, when similar rats were tested more than 2 weeks following surgery these lesions reduced a different form of SIA that was blocked by naltrexone. There were no effects of the lesions or naltrexone on baseline pain reactivity in any of the experiments. We suggest that arcuate nucleus lesions disrupt a system important for the elaboration of opiate-mediated SIA (Expt. 4), perhaps by damaging the brain's beta-endorphin system. In response to damage to this opioid analgesic system, we hypothesize that the damaged brain initiates time-dependent compensatory changes in an undamaged non-opioid analgesic system, resulting in enhanced non-opiate-mediated SIA.

Topics: Analgesia; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Biotin; Body Weight; Drinking Behavior; Electroshock; Endorphins; Feeding Behavior; Male; Naltrexone; Pain; Rats; Rats, Inbred Strains; Stereotaxic Techniques; Stress, Psychological; Wheat Germ Agglutinins

We have recently shown that in addition to beta-endorphin the opioid peptides Met- and Leu-enkephalin and their apparent precursors are localized in islet endocrine cells of the rat pancreas. To begin evaluating a possible role for these pancreatic opiates in the pathophysiology of genetic diabetes in rodents, immunoreactive beta-endorphin and Met- and Leu-enkephalins were measured in acetic acid extracts of pancreas and pituitary of C57BL/KsJ db/db mice and their lean littermates. Groups of animals were studied during three phases of development of the diabetic syndrome in the mutant mice: at 4 (hyperinsulinemic and prediabetic); 6, 9, and 12 (frankly obese and diabetic); and 30 (hypoinsulinemic) wk of age. Elevations or decreases (P less than .05) were found in db/db mice (vs. lean littermates) as follows: pituitary content of Met-enkephalin was twofold higher at all ages studied; pituitary free Leu-enkephalin was lower at 4 wk and reversed to higher at 6-30 wk; pancreatic beta-endorphin was 30% lower at 4 wk and reversed to threefold higher at 6-12 wk; Met- and Leu-enkephalin-containing larger peptides were elevated at one or more points between 6 and 12 wk in both the pancreas and the pituitary. Thus, the onset of overt obesity between 4 and 6 wk of age was accompanied by a marked rise in both pancreatic beta-endorphin and pituitary Leu-enkephalin; similar elevations in these parameters have been reported previously in C57BL/6J ob/ob mice at approximately 12 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; beta-Endorphin; Body Weight; Diabetes Mellitus, Experimental; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Insulin; Islets of Langerhans; Mice; Mice, Obese; Pituitary Gland

Developmental and long-term behavioral effects of perinatal injection of beta-endorphin (BE), CRF and Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1) in male rats were investigated along with the possibility that opiate receptors may be altered by the injection of BE during this critical time. Daily injections of peptide were given to pregnant females (100 micrograms/rat) in the week before birth or to the offspring (50 micrograms/rat) of untreated mothers during the first week of life. Prenatal BE and CRF reduced body weight on day 1, in contrast to Tyr-MIF-1 which produced a significant increase over controls by day 7 as well as a slight but significant acceleration of eye opening. Among the postnatal treatments, CRF-treated animals showed the most dramatic changes. These included decreased body weight, accelerated eye opening, and, in adulthood, increased open field rearing behavior and a tendency for a monotonic body temperature response to low doses of morphine, in contrast to the biphasic response shown by controls. BE, when given to pregnant mothers, increased the number (Bmax) of [3H]naloxone-labeled (mu) receptors in whole brains of offspring assayed on day 14, but it did not significantly alter [3H]D-Ala-D-Leu-enkephalin-labeled (delta) receptors. In contrast, a significant decrease in both mu and delta receptors was observed on day 14 in rats given BE postnatally. These differences in receptors were no longer apparent in adulthood, and no significant differences in tail-flick response were detectable at this time. Nevertheless, some of the effects of these three peptides endured well beyond their presence, and for BE included changes in the number of opiate receptors.

Topics: Animals; Behavior, Animal; beta-Endorphin; Body Weight; Brain Chemistry; Corticotropin-Releasing Hormone; Endorphins; Female; Growth; MSH Release-Inhibiting Hormone; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu

Opioid peptides in the brain are postulated to mediate the hunger component of the control of food intake and regulation of body weight and concentrations are increased in the pituitaries of genetically obese rodents. However, systemic increases in opioids have been associated with satiety. Thus a chronic decrease in systemic concentrations of the opioid beta-endorphin induced by autoimmunization was predicted to increase food intake and body weight. Zucker obese (n = 20, 568 +/- 13 g) and lean (n = 20, 299 +/- 16 g) rats were autoimmunized against bovine serum albumin (BSA) or BSA conjugated to beta-endorphin (BSA-BE). Eight weeks after immunization serum from BSA-BE rats bound at least 7 times the circulating concentration of beta-endorphin. Food intakes were greater in BSA-BE obese (31.7 vs. 30.4 g/day, p less than 0.001) and lean rats (21.4 vs. 21.0 g/day, p less than 0.007) during weeks 5-8 and only obese rats, weeks 9-12 (31.8 vs. 30.3 g/day, p less than 0.009). Body weight gains were greater for BSA-BE than BSA obese rats during weeks 1-4 (1.34 vs. 0.92 g/day, p less than 0.05) and 9-12 (0.95 vs. 0.43 g/day, p less than 0.01). At 8 weeks the plasma concentrations of "free" beta-endorphin were decreased 78% (34 vs. 154 pmol/l, p less than 0.001) and "total" ("free" plus antibody-bound) beta-endorphin were increased (427 vs. 101 pmol/l, p less than 0.001). These results suggest that systemic concentrations of beta-endorphin may play an important role in the control of food intake and regulation of energy balance.

Topics: Animals; Autoantibodies; beta-Endorphin; Body Weight; Eating; Endorphins; Female; Hypothalamus; Male; Obesity; Pituitary Gland; Protein Binding; Rats; Rats, Zucker

Patterns of normal and stimulated food intake (FI) as well as its possible endogenous opioid (EO) modulation were investigated in male rats given regular swimming exercise (trained; TR) and compared with nonexercised sedentary (SED) controls. Rats in the TR group had lower body weights as well as reduced 24 hr FI due to lower nocturnal FI. TR rats also ate less food in response to injections of 2-deoxy-D-glucose (2-DG) but not insulin (INS) when injections were given during the first 4-5 weeks of training. However, this difference between TR and SED rats in the 2-DG induced feeding was not demonstrable after 10 or more weeks of training. Plasma concentrations of immunoreactive B-endorphin (IR-B-ep) were elevated, as expected, in TR rats (10-12 weeks) during nocturnal sampling whereas the nocturnal increase of IR-B-ep was absent in SED controls. However, these SED rats did increase daytime IR-B-ep in response to 2-DG and acute exercise, albeit somewhat less in magnitude when compared to TR rats. Injection of naltrexone (NTX) decreased feeding in TR rats (10-12 weeks) but not in contemporary SED controls. In summary, exercise training modified feeding behavior, and at 4 weeks of training, TR rats ate less in response to opioid-related feeding stimulus of 2-DG, but responded similarly to insulin (relatively opioid independent) treatment. At later stages of training this difference between TR and SED rats disappeared. Moreover, SED rats had atypical profiles of IR-B-ep and reduced hypophagic responses to NTX suggesting that TR rats might have greater EO modulation of feeding at this stage.

Topics: Animals; beta-Endorphin; Body Weight; Circadian Rhythm; Deoxyglucose; Endorphins; Feeding Behavior; Insulin; Male; Naltrexone; Physical Exertion; Rats; Rats, Inbred Strains; Swimming; Time Factors

The antigonadal activity of potent gonadotropin-releasing hormone (GnRH) analogs may be associated with undesirable secondary effects on other aspects of the endocrine system. In preliminary studies, rats treated with GnRH agonists were noted to have altered adrenal weights. To determine whether this was associated with alterations in the pituitary-adrenal axis we have studied male and female rats treated with the GnRH agonist [(imBzl)-D-His6, Pro9-NEt]-GnRH (GnRH-A). Animals receiving daily doses of this peptide showed normal adrenal corticosteroid responsivity to both ether and immobilization stress. Brain, pituitary, and plasma concentrations of immunoreactive (IR) beta-endorphin and ACTH were unaffected in treated animals after four weeks of daily injections, although after one week plasma levels of the two hormones were transiently elevated in female rats. Adrenal, thyroid, and pituitary lobe weights were unchanged with treatment, except for an increase in anterior pituitary weight in males receiving the lowest dose of GnRH-A. In conclusion, long-term treatment with GnRH-A, while significantly affecting gonadal and secondary sexual tissue, had little impact on the hypothalamo-pituitary-adrenal system or on stress responsivity in rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Castration; Corticosterone; Endorphins; Ether; Female; Gonadotropin-Releasing Hormone; Hypothalamus; Immobilization; Male; Pituitary Gland; Rats; Rats, Inbred Strains; Stress, Physiological

Lower concentrations of immunoreactive (IR) beta-endorphin were present in the neurointermediate pituitary lobes of streptozocin-induced diabetic versus control animals at both 2 and 4 weeks after the onset of diabetes. The forms of beta-endorphin-like material present appeared to be similar in both groups when studied with cation-exchange chromatography. Insulin therapy via minipump for 2 weeks did not alter this finding of lowered beta-endorphin concentrations in diabetic animals, despite normalization of blood glucose levels and body weight gain. Lower IR beta-endorphin levels were also found in neurointermediate lobes of weight-restricted rats, but this group had increased plasma IR beta-endorphin concentrations compared to diabetic animals. Concentrations of IR beta-endorphin in microdissected brain regions and in anterior pituitaries of the diabetic animals failed to show consistent changes; in addition, ACTH concentrations in pituitary lobes and plasma did not differ among groups. Circadian rhythmicity of plasma insulin and corticosterone concentrations was absent in the diabetic animals, although food and water intake, while elevated, showed the normal nocturnal pattern of increased ingestion. Furthermore, adrenal hypertrophy was present in the diabetic animals and was accompanied by an elevation of mean plasma corticosterone levels. The present findings indicate that diabetes is associated with a decrease of neurointermediate pituitary lobe synthesis of beta-endorphin, while not affecting the processing of the peptide in this lobe, and confirm previous reports of altered adrenal function in diabetic animals.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Body Weight; Brain; Chromatography; Circadian Rhythm; Corticosterone; Diabetes Mellitus, Experimental; Drinking; Eating; Endorphins; Insulin; Male; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains; Tissue Distribution

Young and mature, genetically obese and non-obese, spontaneously hypertensive rats (SHR) were injected with saline (controls) or naloxone for 12 weeks. Naloxone stilled the hyperphagia to a normal intake in the obese SHR (Obese/SHR) so that young Obese/SHR did not develop their usual massive obesity and mature Obese/SHR that had become massively obese were reduced to leanness. The naloxone-treated young, obese and non-obese SHR (controls) exhibited marked reduction of the weight of their pituitary and adrenal glands, whereas the pituitary and adrenal glands of naloxone-treated mature, obese and non-obese/SHR were greatly increased in weight. The elevated systolic blood pressure of the obese and non-obese rats was reduced after chronic treatment with naloxone. Naloxone treatment caused reduction of blood ACTH, corticosterone, and beta endorphin levels but elevated growth hormone levels. The characteristic hyperinsulinemia, hyperlipidemia, hyperglycemia, elevated BUN levels, and the Cushingoid spectrum of degenerative changes found in Obese/SHR did not appear in naloxone-treated rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Pressure; Body Weight; Corticosterone; Cushing Syndrome; Disease Models, Animal; Endorphins; Female; Growth Hormone; Male; Naloxone; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred SHR; Rats, Inbred Strains

The relationship of endogenous opiates in patients with polycystic ovarian disease (PCOD) and their influence on body weight was studied. The study group consisted of 19 women with PCOD. They were amenorrheic, hirsute, and hyperandrogenic, and their average weight was 124% of the ideal body weight. They had luteinizing hormone/follicle-stimulating hormone ratios greater than or equal to 2. The control group consisted of ten women with regular ovulatory menses. Plasma beta-endorphin (beta-EP) was measured by using a very specific radioimmunoassay. beta-Lipotropin (beta-LPH) was entirely removed from the sample by preincubation of the plasma with rabbit anti-beta-LPH/Sepharose complex (Pharmacia, New Brunswick, NJ). The mean +/- standard deviation of the plasma beta-EP in the control group was 70.18 +/- 18.06 pg/ml, and the mean +/- standard deviation of beta-EP in the study group was 185.6 +/- 93.4 pg/ml, which was significantly higher than the control levels (P less than 0.001). A significant correlation was also found between plasma beta-EP level and the patient's weight in the PCOD group (r = 0.462, P = 0.025). The data from this study suggest that the elevated levels of endogenous opiates may be involved in the pathophysiology of PCOD and be related to inappropriate secretion of gonadotropins influencing body weight.

Topics: Adolescent; Adult; Amenorrhea; beta-Endorphin; Body Weight; Endorphins; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Polycystic Ovary Syndrome; Radioimmunoassay

Competitive swimmers were followed over a 2-year period when they trained at different levels of exercise which coincided with distinct changes in their menstrual history. Oligomenorrhea was identified in 5 of 13 of these athletes when they swam approximately 100,000 yards per week. Weight and percentage of body fat were not significantly different between the period of oligomenorrhea and regular menstrual function (P = 0.24). Mean and median levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and 17beta-estradiol were decreased and catechol estrogens and beta-endorphins were increased in serum during the strenuous, when compared with the moderate, training period. The serum levels of the steroid and protein hormones were similar to those of normal cycling, nonexercising control subjects during moderate exercise (60,000 yards per week). The significant differences between beta-endorphins and catechol estrogens during periods of strenuous exercise suggest an explanation for oligomenorrhea in female athletes. These hormonal changes result in hypothalamic anovulation, which appears to be reversible, because the hormone levels and menstrual cycles return to normal when the exercise is reduced.

Topics: Adolescent; Adult; beta-Endorphin; Body Composition; Body Weight; Endorphins; Estradiol; Estrogens, Catechol; Female; Follicle Stimulating Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Menstruation Disturbances; Oligomenorrhea; Physical Exertion; Prolactin; Sports Medicine; Swimming

Pituitary beta-endorphin content was measured in dormice during several distinct phases of the infradian body weight cycle. No significant differences in opiate content among groups were found. It appears unlikely that pituitary concentrations of beta-endorphin have etiological significance in the development of spontaneous obesity in hibernators.

Topics: Animals; beta-Endorphin; Body Weight; Endorphins; Feeding Behavior; Female; Humans; Male; Periodicity; Pituitary Gland; Rodentia; Species Specificity

The contents of immunoreactive somatostatin (IR-SRIF) and beta-endorphin (IR-beta-EP) in 12 brain regions were examined in rats exposed neonatally to propylthiouracil (PTU) through the mother's milk. Since the dose of PTU used in this study is lower than the usual dose employed to induce hypothyroidism, a milder form of neonatal hypothyroidism resulted. This conclusion is supported by the only mild subnormal growth of rats to adulthood and serum T4 and T3 concentrations in the normal range. Adult rats treated with PTU neonatally had significantly higher IR-SRIF contents in several brain regions compared to controls, whereas IR-beta-EP levels were not significantly different (significant increase only in the thalamus) in most regions. The results indicate that even mild hypothyroidism during early postnatal development causes permanent impairment of brain function, which manifests itself in part by an altered brain content of IR-SRIF.

Topics: Animals; beta-Endorphin; Body Weight; Brain Chemistry; Endorphins; Female; Male; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Rats; Somatostatin; Thyroxine; Tissue Distribution; Triiodothyronine

D-Fenfluramine, an anorectic that releases serotonin (5-HT), repeatedly injected in rats (15 mg/kg per day) enhanced the met5-enkephalin and beta-endorphin content of the hyhpothalamus. The onset of this effect was slow, reaching a peak at 5 days; the increase in beta-endorphin gradually declined toward control level while the drug was still being administered although that of met-enkephalin persisted for 15 days. The elevation of the opioid peptide content of the hypothalamus was temporally associated with a slowing in the rate of body weight increase. A transient, small, increase in striatal met-enkephalin content was also induced by repeated D-fenfluramine injections; however the met-enkephalin content of frontal cortex, hippocampus and brainstem was not affected. A modification of the beta-endorphin content of hypothalamus was not seen after acute injection of D-fenfluramine or D-amphetamine but an increase was observed during repeated treatment with D-fenfluramine. Repeated injections of D-amphetamine for 5 days (4.5 mg/kg per day) failed to increase either the met-enkephalin or the beta-endorphin content of the hypothalamus. These data suggest that the anorexia elicited by repeated injections of D-fenfluramine but not that elicited by D-amphetamine, includes a participation by hypothalamic and beta-endorphin stores.

Topics: Animals; beta-Endorphin; Body Weight; Brain; Dextroamphetamine; Endorphins; Enkephalin, Methionine; Enkephalins; Fenfluramine; Hypothalamus; Male; Rats; Rats, Inbred Strains; Stimulation, Chemical; Time Factors

Immunoreactive ACTH (ir-ACTH) and immunoreactive beta-endorphin (ir-betaEP) were determined in plasma, anterior pituitary, neuro-intermediate lobe, and hypothalamus of sham-adrenalectomized rats, and adrenalectomized rats given six daily injections of vehicle (oil), dexamethasone, 9alpha-fluorocortisol or deoxycorticosterone. 6 d after adrenalectomy, anterior pituitary ir-ACTH and ir-betaEP were double, and plasma levels approximately fivefold those in controls. Adrenalectomy did not alter hypothalamic levels of either peptide, or ir-betaEP in neuro-intermediate lobe, in which tissue ir-ACTH was below detection limit at routine dilutions. Dexamethasone (0.2-200 mug/d) concurrently suppressed plasma ir-ACTH and ir-betaEP, with a near maximal effect at 20 mug, and a half-maximal effect between 2 and 6 mug; similar dose-response characteristics were found for thymolysis. Step-wise increases in anterior pituitary content of both peptides were found, with no change in hypothalamic levels of either peptide, or neuro-intermediate lobe ir-betaEP. 9alpha-fluorocortisol (0.2-200 mug/d) produced plasma, anterior pituitary, and hypothalamic effects equivalent to dexamethasone, but with one-tenth the potency. Unlike dexamethasone, higher doses of 9alpha-fluorocortisol significantly elevated neuro-intermediate lobe ir-betaEP. Deoxycorticosterone (2-2,000 mug/d) produced no significant changes in plasma, anterior pituitary or hypothalamic levels of either peptide; like 9alpha-fluorocortisol, doses of >60 mug/d significantly elevated neuro-intermediate lobe ir-betaEP. Whereas ir-ACTH and ir-betaEP synthesis in and release from the anterior pituitary are under complex negative feedback glucocorticoid control, there exists a mineralocorticoid-specific effect on neuro-intermediate lobe content of ir-betaEP.

Topics: Adrenal Glands; Adrenalectomy; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Body Weight; Desoxycorticosterone; Dexamethasone; Endorphins; Female; Fludrocortisone; Hypothalamus; Organ Size; Pituitary Gland, Anterior; Rats; Rats, Inbred Strains

Topics: Animals; beta-Endorphin; Body Weight; Cricetinae; Drinking; Endorphins; Enkephalin, Methionine; Ethanol; Hypothalamus; In Vitro Techniques; Mesocricetus; Pituitary Gland; Rats; Rats, Inbred Strains; Species Specificity; Time Factors

Effects of intravenous beta-endorphin on body temperature and body weight loss were studied in naive and morphine-dependent mice. beta-Endorphin at doses 2.6-25.5 mg/kg injected intravenously caused hyperthermia in naive mice as well as in morphine-dependent mice. In addition, beta-endorphin and morphine reduced body-weight loss during the morphine withdrawal.

Topics: Animals; beta-Endorphin; Body Temperature; Body Weight; Drug Interactions; Endorphins; Fever; Injections, Intravenous; Male; Mice; Morphine

Naltrexone, an opiate antagonist, was administered to young obese (ob/ob) and lean mice for five weeks. Animals had continuous access to food and received 10 mg/kg SC twice daily with equivalent volumes of saline given to controls. The effects on body weight, and pituitary and plasma levels of beta-endorphin-like material were measured. Naltrexone-injected obese animals gained weight more slowly over the first three weeks while the weight gain of lean animals was not affected by naltrexone. Plasma levels of beta-endorphin were shown to be significantly higher in untreated ob/ob mice and this difference increased with age (4-20 weeks). With naltrexone treatment, plasma levels in +/? mice rose and exceeded those in ob/ob. Saline treatment appeared to be a stress, and pituitary beta-endorphins rose 4-6 fold in ob/ob compared with +/?. While naltrexone reduced the levels of ob/ob pituitary towards normal, no effect on beta-endorphin levels in pituitary of lean mice was obtained. In vitro studies of effects of the opiate antagonists, naloxone, on insulin secretion by isolated islets provided additional evidence of resistance of lean mice to naloxone relative to ob/ob. (IRI secretion fell only in naloxone treated ob/ob islets). These observations support the contention that this form of genetic obesity is characterized by elevated endogenous opiate levels and an increased sensitivity to opiate antagonists such as naltrexone or naloxone.

Topics: Animals; beta-Endorphin; Body Weight; Endorphins; Insulin; Insulin Secretion; Islets of Langerhans; Mice; Mice, Obese; Naloxone; Naltrexone; Obesity; Pituitary Gland; Receptors, Opioid