naloxone and Starvation

Starvation is associated with a blunted TSH response to thyrotropin-releasing hormone (TRH) (peak minus baseline < 5 mIU/L), despite basal TSH and thyroid hormone levels within the normal range. In light of the inhibitory effect of somatostatin on TSH secretion, we examined whether this condition is caused by an increased hypothalamic somatostatinergic tone in starving subjects. The possible involvement of endogenous opioids in the mechanism underlying the abnormal TSH response to TRH was also evaluated.. The TSH response to TRH (25 micrograms in an intravenous bolus), serum total and free T4 and T3 levels, and 24-hour urinary-free cortisol levels were measured in 28 normal men (age 27-35 years) within 10% of their ideal body weight. They were randomly divided into 4 groups of 7. In 21 subjects (groups 1, 2, and 3), TRH tests were performed after an overnight (8 hours) fast, placebo administrations (control test), and after prolonged (56 hours) starvation. TRH tests after prolonged starvation were performed either after placebos (in all subjects) or the administration of pyridostigmine (180 mg orally) (in 7 subjects, group 1); naloxone (0.8 mg in an i.v. bolus injection) (in 7 subjects, group 2); or the combination of pyridostigmine and naloxone (in 7 subjects, group 3). The remaining 7 subjects (group 4) were tested at weekly intervals with TRH plus placebo, TRH plus naloxone, TRH plus pyridostigmine, and TRH plus naloxone plus pyridostigmine after a fasting period of 8 hours.. In all subjects of groups 1, 2, and 3, TRH-induced TSH rise was significantly lower after prolonged starvation than after overnight fast. Neither pyridostigmine nor naloxone, given alone, changed the basal levels of TSH and the TSH response to TRH after prolonged starvation. In contrast, the concomitant administration of naloxone and pyridostigmine significantly enhanced the TRH-induced TSH rise. After overnight fasting, naloxone administration in group 4 subjects did not change the TSH response to TRH, whereas pyridostigmine significantly enhanced the TSH response to TRH. When naloxone was given together with pyridostigmine and TRH the TSH response was similar to that observed in the TRH plus pyridostigmine test.. These data indicate that naloxone-sensitive endogenous opioids exert an inhibitory effect on the cholinergic stimulatory control of TSH secretion during prolonged starvation. This suggests that an enhanced hypothalamic somatostatinergic activity is involved in the mechanism underlying the reduced TSH response to TRH.

Topics: Adult; Humans; Hypothalamo-Hypophyseal System; Male; Naloxone; Narcotic Antagonists; Parasympathomimetics; Pyridostigmine Bromide; Somatostatin; Starvation; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.

Topics: Amino Acid Sequence; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Conserved Sequence; Feeding Behavior; Gene Expression Regulation; Molecular Sequence Data; Morphine; Naloxone; Neurons; Neuropeptides; Receptors, Opioid; Signal Transduction; Starvation

Testosterone (T) levels necessary to suppress LH secretion are reduced in starvation, and increased feedback sensitivity to T is therefore postulated. The luteinizing hormone (LH) response to naloxone (Nal) is more easily suppressed by starvation than is its response to prostaglandin E2 (PGE2) and to luteinizing hormone-releasing hormone (LRH). If the divergent suppressibility is due to altered feedback sensitivity in starvation, it should be feasible to reproduce this phenomenon in normally nourished rats by increasing T levels. Adult male Wistar rats were castrated and implanted with silicone capsules (0-2.6 cm) filled with T. Indwelling jugular cannulae were implanted. On days 4 to 8 post operation rats were injected iv with LRH (25-400 ng/kg body weight), PGE2 (0.05-1.0 mg/kg body weight) or Nal (0.5-50 mg/kg body weight). Blood samples were drawn before and 10, 20 and 30 min after injection. Results show that the response to Nal was already suppressed at medium T levels. The LH response to PGE2 was diminished to a greater extent than the response to LRH but was never completely suppressed by increasing steroid levels. These data are compatible with the hypothesis that steroid feedback sensitivity augments with increasing levels of regulation of the hypothalamic-pituitary-gonadal axis.

Topics: Animals; Dinoprostone; Drug Implants; Feedback; Gonadotropin-Releasing Hormone; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Naloxone; Orchiectomy; Prostaglandins E; Rats; Rats, Inbred Strains; Starvation; Testis; Testosterone

Modulation of feeding by opiates, putative satiety peptides, and dopamine was explored in the Chinese hamster, an animal that develops diabetes mellitus in certain inbred strains. Diabetic hamsters were hyperphagic relative to their nondiabetic controls, but both groups exhibited natural circadian variation in feeding. Starvation provoked hyperphagia of about 1-h duration in both groups. Naloxone and butorphanol had no effects on Chinese hamster feeding. Opiate receptor binding on Chinese hamster brains demonstrated no specific binding of naloxone or ethylketocyclazocine, but IR-dynorphin concentrations were comparable with that in rats. N-allylnormetazocine, a sigma-opiate receptor agonist, appeared to stimulate diabetic hamster feeding. Peptides reputed to have satiety effects in rats were without effect in Chinese hamsters: cholecystokinin, bombesin, somatostatin, and pancreatic polypeptide. Calcitonin limited feeding in both groups but may be nonspecific. Dopaminergic blockade by haloperidol also limited feeding, and diabetic hamsters were more sensitive to this. Although Chinese hamsters clearly can modulate their food intake when diabetic, we conclude that the opiatergic and peptidergic influences on feeding are very different from those in rats and may be of little importance.

Topics: Animals; Brain; Calcitonin; Circadian Rhythm; Cricetinae; Cyclazocine; Diabetes Mellitus; Dynorphins; Eating; Endorphins; Ethylketocyclazocine; Feeding Behavior; Haloperidol; Mesocricetus; Naloxone; Peptide Fragments; Phenazocine; Sincalide; Starvation

In man and other mammals, starvation is accompanied by a severe suppression of luteinizing hormone-releasing hormone (LHRH) and luteinizing-hormone (LH) secretion, which is caused by unknown alterations in hypothalamic functions. Prostaglandin E2 (PGE2), endorphins and testosterone (T) are know to be strongly involved in the regulation of LHRH release. The present study examined whether the influence of these substances on LHRH and LH secretion was affected by starvation. In vitro experiments checked the release of PGE2 and LHRH from median eminences (ME) of fed male rats and ones starved for 5 days. Stimulation with potassium (80 mM) induced an equally strong release of PGE2 and LHRH from the MEs of both fed and starved rats. When PGE2 (10(4) M) was added to the superfusion medium, the potassium-stimulated release of LHRH was significantly enhanced in both groups of animals. The results clearly showed that in the terminal region of the hypothalamic LHRH system the release of this hormone and the action of PGE2 were not altered by starvation. In vivo experiments tested whether the effects of LHRH, PGE2, naloxone (NAL), or T on LH secretion were different in intact or castrated male rats fed or starved for 3 and 5 days. LHRH (250 ng/kg) stimulated the same amount of LH secretion in fed and starved rats. The starvation-induced LH suppression was not due to a dysfunction at the pituitary level. The stimulatory action of PGE2 (1 mg/kg) on LH was gradually reduced throughout the starvation period. NAL (5 mg/kg) had little, respectively, no effect on LH release on the 3rd or 5th day of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Castration; Feedback; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Median Eminence; Naloxone; Pituitary Gland; Potassium; Prostaglandins E; Rats; Rats, Inbred Strains; Starvation; Stimulation, Chemical; Testosterone

Topics: Animals; Circadian Rhythm; Cyclazocine; Eating; Ethylketocyclazocine; Male; Morphine; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, kappa; Starvation; Time Factors

Topics: Alcoholism; Animals; Corticosterone; Disease Models, Animal; Ethanol; Humans; Male; Naloxone; Rats; Starvation; Time Factors