naloxone and Pituitary-Neoplasms

The expression pattern of the opioid receptor (MOR) in pituitary neuroendocrine tumors (PitNET) and the possible effect of morphine and naloxone on GH3 cell growth and apoptosis were evaluated.. The 114 pituitary tissues including non-functioning, GH-producing and ACTH-producing PitNET and healthy cadaver pituitary tissues were included. The expression level of the MOR gene and protein was assessed using real-time PCR and Western blot. The association with patient demographic characteristics was assessed. Morphine and naloxone were applied to assess their possible pharmacological role in GH3 pituitary adenoma cell death. The cytotoxic effect, the apoptosis rate, the cell cycle distribution, the content of reactive oxygen species and the caspase 3 activity were measured.. MOR gene levels increased significantly in pituitary neuroendocrine tumors (PitNET) compared to the healthy pituitary samples. The increased level of MOR gene expression was prominent in invasive functional and non-functional pituitary tumors. A consistent expression pattern was demonstrated for MOR protein levels in PitNET samples. A dose- and time-dependent reduction in the rate of GH3 pituitary cells was observed after morphine treatment with an IC50 of 483 µM after 24 h of incubation. Morphine induced early apoptosis, accumulation of cells in sub-G1 phase, increase in cellular ROS levels and caspase-3 activity. The observed effects of morphine were reversed after MOR blockade using 10 and 25 µM naloxone.. The possible contributing role of the MOR in pituitary tumor cell growth and the putative pharmaceutical effect of morphine in pituitary neuroendocrine tumor cell death (PitNET) is illustrated.

Topics: Apoptosis; Cell Cycle; Cell Line; Humans; Morphine; Naloxone; Narcotic Antagonists; Neuroendocrine Tumors; Pituitary Neoplasms; Receptors, Opioid; Receptors, Opioid, mu

The purpose of the present study was to gain a better insight in the mechanism of naloxone underlying the regulation of adrenal cortisol secretion in humans in vivo; therefore, the stimulatory effect of naloxone on cortisol secretion was assessed in a group of patients with hypothalamo-pituitary disconnection. Patients with hypothalamo-pituitary disconnection because of various pathologies (craniopharingioma, cordoma, suprasellar meningioma, or pituitary macroadenoma) participated in the study.. Circulating cortisol, but not adrenocorticotropin (ACTH) levels were significantly higher after naloxone administration than after saline.. Besides the well-known hypothalamo-pituitary stimulatory action on ACTH release in normal humans, the results of the present study suggest that naloxone exerts direct effects on cortisol secretion at the adrenal gland level; another possibility is that naloxone stimulation of cortisol secretion is mediated by other factor than ACTH.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Adult; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Naloxone; Pituitary Neoplasms

Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains unclear. The effects of Mtd and its two main metabolites (EDDP: (±)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3-dipnehyl-1-pyrroline) on ion currents were investigated in GH₃ pituitary tumor cells. Hyperpolarization-elicited K+ currents in GH₃ cells bathed in a high-K(+), Ca(2+)-free solution were studied to evaluate the effects of Mtd and other related compounds on the ether-à-go-go-related-gene (erg) K(+) current (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration-dependent manner with an IC(50) value of 10.4 μM. With the aid of a minimal binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a dissociation constant of 8.2 μM. Mtd tended to increase the rate of I(K(erg)) deactivation in a voltage-dependent fashion. EDDP (10 μM) had no effect on I(K(erg)), while EMDP (10μM) slightly suppressed it. In GH₃ cells incubated with naloxone (30 μM), the Mtd-induced inhibition of I(K(erg)) remained unaltered. Under cell-attached voltage-clamp recordings, Mtd increased the frequency of spontaneous action currents with no change in current amplitude. Similarly, Mtd can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a depressant effect on I(K(erg)), and suggests its ability to affect membrane excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+ channel.

Topics: Animals; Cell Line, Tumor; Ether-A-Go-Go Potassium Channels; Methadone; Naloxone; Narcotics; Neurons; Pituitary Neoplasms; Prolactin; Pyrrolidines; Rats; Risperidone

To study the reliability of the naloxone test in assessing the hypothalamic-pituitary-adrenal (HPA) axis in patients following transsphenoidal pituitary surgery, by comparison with the insulin stress test (IST). Also, to establish a normal range for the response to naloxone in healthy controls.. All patients had the IST performed, soluble insulin 0.1-0.3 U/kg (usually 0.15 U/kg) being administered intravenously, followed by venous sampling for plasma glucose and serum cortisol at 0, 15, 30, 45, 60, 75 and 90 minutes. Naloxone (125 micrograms/kg body weight) was similarly administered to all patients 6 days later, with sampling at -15, 0, 15, 30, 45, 60, 90 and 120 minutes for plasma glucose, serum cortisol and plasma ACTH. The naloxone test was also performed on control subjects using an identical protocol.. Twenty patients (11F/9M) aged 48.8 +/- 2.8 years (mean +/- SE) 4-6 weeks following transsphenoidal pituitary surgery. Twelve normal healthy control subjects (6F/6M) aged 31.5 +/- 3.0 years.. Serum cortisol was measured by radioimmunoassay and plasma ACTH by immunoradiometric assay.. Adequate hypoglycaemia (< or = 2.0 mmol/l) was achieved in all patients. Peak cortisol was > 550 nmol/l in 17 subjects (range: 572-867 nmol/l) and a subnormal response observed in 3 (peak cortisol 163-498 nmol/l). In the 17 patients with a normal cortisol response to hypoglycaemia the response to naloxone was extremely variable, with serum cortisol falling in 4 and an increment of < or = 100 nmol/l in 6 others. In the 3 patients who failed the IST, two responded to naloxone and one did not. In normal controls, 3 of the 12 had little or no response to naloxone.. As the naloxone test fails to produce a response in all normal subjects it is impossible to define a 'normal' response. The numerous discrepancies with the IST in patients are further evidence of the test's lack of reliability in assessing the HPA-axis and it is consequently not a viable alternative to traditional dynamic methods such as the IST.

Topics: Adrenocorticotropic Hormone; Case-Control Studies; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Middle Aged; Naloxone; Narcotic Antagonists; Pituitary Neoplasms; Pituitary-Adrenal System; Postoperative Period; Reproducibility of Results

To determine the role of opioidergic and dopaminergic activity in the suppression of GnRH0LH in a hyperprolactinemic state.. Case report.. University hospital.. A 68-year-old woman with a macroprolactinoma.. Serial 10-hour IV infusions of naloxone and metoclopramide.. Serum LH concentration.. Naloxone induced a small but significant rise of serum LH levels, which displayed a pulsatile pattern. By contrast, metoclopramide elicited no significant response in LH secretion.. Opioidergic but not dopaminergic neurotransmission plays a direct role in the suppression of LH secondary to hyperprolactinemia.

Topics: Aged; Bromocriptine; Dopamine Agonists; Dopamine Antagonists; Female; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Hypogonadism; Injections, Intravenous; Luteinizing Hormone; Metoclopramide; Naloxone; Narcotic Antagonists; Pituitary Neoplasms; Postmenopause; Prolactin; Prolactinoma

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.

Topics: Acromegaly; Adenoma; Adult; Growth Hormone; Headache; Humans; Male; Naloxone; Octreotide; Pain, Intractable; Pituitary Neoplasms; Receptors, Opioid

The ability to change the frequency and amplitude of pulsatile GnRH secretion may be an important mechanism in maintaining regular ovulatory cycles. Hyperprolactinemia is associated with anovulation and slow frequency LH (GnRH) secretion in women. To assess whether the slow frequency of LH (GnRH) secretion is due to increased opioid activity, we examined the effect of naloxone infusions in eight amenorrheic hyperprolactinemic women (mean +/- SE, serum PRL, 160 +/- 59 micrograms/L). After a baseline period, either saline or naloxone was infused for 8 h on separate days, and LH was measured in blood obtained at 15-min intervals. Additional samples were obtained for plasma FSH, PRL, estradiol, and progesterone. Responses to exogenous GnRH were assessed at the end of the infusions. LH pulse frequency increased in all subjects from a mean of 4.0 +/- 0.5 pulses/10 h (mean +/- SE) during saline infusion to 8.0 +/- 1.0 pulses/10 h during naloxone infusion (P less than 0.01). LH pulse amplitude did not change, and mean plasma LH increased from 7.4 +/- 0.8 IU/L (+/- SE) to 11.2 +/- 1.5 IU/L during naloxone (P less than 0.01). A small but significant increase was seen in mean plasma FSH. Plasma PRL, estradiol, and progesterone were unchanged by naloxone infusion. These data suggest that elevated serum PRL reduces the frequency of LH (GnRH) secretion by increasing hypothalamic opioid activity and suggest that the anovulation in hyperprolactinemia is consequent upon persistent slow frequency LH (GnRH) secretion.

Topics: Adult; Amenorrhea; Circadian Rhythm; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin

The investigators assessed the effects of the opioid antagonist naloxone on anterior pituitary hormone release in hyperprolactinemic females with pituitary microadenoma (n = 6) and macroadenoma (n = 7). In those with microadenoma, intravenous bolus injection of naloxone significantly increased serum luteinizing hormone (LH) concentrations but had no significant effect on serum prolactin (PRL), follicle-stimulating hormone, and thyroid-stimulating hormone concentrations. In patients with macroadenoma, naloxone significantly decreased serum LH and serum PRL concentrations. The response of LH to naloxone differed considerably between the two groups of patients. The results suggest that LH and PRL secretion is influenced by changes in endogenous opiates and in gonadotropin-releasing hormone and PRL inhibitory factor due to hypothalamic dysfunction.

Topics: Adenoma; Adolescent; Adult; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin; Thyrotropin

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.

Topics: Adenoma; Adult; Amenorrhea; Antipsychotic Agents; Dopamine Antagonists; Endorphins; Female; Humans; Hyperprolactinemia; Iatrogenic Disease; Luteinizing Hormone; Menopause; Metoclopramide; Naloxone; Pituitary Neoplasms; Schizophrenia

Although hyperprolactinemia has been reported to decrease reproductive function in male rats, the mechanism of these effects is not fully understood. We examined the effects of chronic hyperprolactinemia and castration on the LHRH content of the medial basal hypothalamus (MBH) and on the basal and evoked in vitro release of LHRH from the MBH-preoptic area (POA). Adult Wistar-Furth male rats were inoculated with MtTW15 tumor fragments; 3 weeks later half of the rats were castrated. Hyperprolactinemic (H) and normoprolactinemic (N) rats were decapitated 2 weeks later to measure MBH LHRH and serum PRL and LH levels. Elevated PRL levels (greater than 2 micrograms/ml) resulted in significantly increased MBH LHRH stores. Castration caused a 57% depletion of MBH LHRH in N rats; in castrated H rats the MBH LHRH content was also reduced by 40%, a significantly lesser extent. Although serum LH levels in intact H rats were only slightly reduced, postcastration LH hypersecretion was significantly attenuated. In a parallel study, the LHRH release rate was assessed by in vitro perfusion of the MBH-POA. The basal LHRH release rates of intact N and H rats were similar. Castrated N rats released LHRH at a reduced rate (50%; P less than 0.01), whereas in castrated H rats the LHRH release rate was reduced by 20%, which corresponded with the partial depletion of the MBH LHRH content in these rats. To examine the possibility of opiate involvement, LHRH release evoked by two consecutive naloxone (NAL) infusions (1 mg/ml for 30 min) was studied. The two NAL infusions resulted in two similar significant increments of LHRH in the MBH-POA of intact N and H rats. However, castration produced different effects on the NAL-induced LHRH release. First, the second NAL pulse was not effective in stimulating LHRH release from the MBH-POA of N and H castrated rats. Further, the first NAL infusion elicited a significant increase in LHRH output from the MBH-POA of N and H castrated rats, but it was significantly lower in comparison with that in their respective intact counterparts. In addition, the NAL-induced LHRH response was higher from the MBH-POA of castrated H than that in castrated N rats. These studies show that neither basal nor evoked LHRH output in vitro is affected by severe and chronic hyperprolactinemia produced by MtTW15 pituitary tumor cells in intact male rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Gonadotropin-Releasing Hormone; Hyperprolactinemia; Hypothalamus; Hypothalamus, Middle; Luteinizing Hormone; Male; Naloxone; Neoplasm Transplantation; Orchiectomy; Pituitary Neoplasms; Potassium; Preoptic Area; Rats; Rats, Inbred WF

The effects of varying the sodium concentration (at constant ionic strength) on opioid binding at mu- and delta-opioid receptors in 7315c and NG108-15 cells has been examined. The binding of [3H]etorphine to mu-receptors on 7315c cells was increased by replacing the sodium in the incubation medium with potassium or N-methyl-D-glucamine. This effect was shown to be attributable to an increase in affinity, with no change in the maximum number of binding sites, both in cell membrane suspensions and in intact 7315c cells. Replacement of sodium with potassium or N-methyl-D-glucamine in NG108-15 membrane or intact cell suspensions also resulted in an increase in [3H]etorphine binding, but in these cells the effect was associated with an increase in the number of binding sites measurable under these experimental conditions. The effects of sodium on opioid inhibition of adenylate cyclase in membrane preparations from 7315c and NG108-15 cells also differed. Sodium reduced apparent agonist affinity in 7315c membranes. In NG108-15 cell membranes, sodium was essential for the demonstration of opioid inhibition of cyclase activity. Increasing the sodium concentration above 0.5 mM resulted in an increase in the fraction of total enzyme activity inhibited by opioid, but the opioid IC50 did not change. In the companion paper, it is shown that the effects of sodium removal on mu- and delta-receptor binding in guinea pig brain neural membranes were similar to those observed in the cell preparations. An increase in intracellular sodium concentration without change in extracellular concentration was effected by incubation of 7315c and NG108-15 cells with the sodium-selective ionophore, monensin. When sodium was present in the extracellular medium, monensin reduced [3H]etorphine binding by 50% or more, both at mu-receptors in 7315c cells and at delta-receptors in NG108-15 cells. In the absence of sodium, however, monensin treatment produced only a small inhibition of binding. These results suggest that sodium acts at an intracellular site to regulate opioid agonist binding at both mu- and delta-receptors, but that the mode of regulation is not identical at each site. Since a reduction in intracellular sodium concentration by removal of extracellular sodium increases agonist binding, and an increase in intracellular sodium following monensin treatment reduces agonist binding, it is probable that the intracellular sodium concentration is a critical regulator of opioid agonist b

Topics: Adenylyl Cyclase Inhibitors; Animals; Cell Line; Cell Membrane; Cyclazocine; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Ethylketocyclazocine; Etorphine; Glioma; Guinea Pigs; Monensin; Naloxone; Neuroblastoma; Pituitary Neoplasms; Rats; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Sodium

Endogenous opiate peptides are considered to inhibit LH secretion via a dopaminergic mechanism, and increased opioid inhibition of LH secretion has been found in some hyperprolactinemic women with a pituitary microadenoma. To assess the role of endogenous dopaminergic tone in the opioid regulation of LH secretion in such patients, LH responses to an opioid antagonist (naloxone) and a dopamine antagonist (metoclopramide) were determined in 11 women with a prolactinoma. Neither naloxone nor metoclopramide administration induced any change in serum LH levels in normal women during the early follicular phase. In contrast, 7 of the 11 hyperprolactinemic women responded to both antagonists with a significant increase in LH levels. The parallelism in the LH responses to both antagonists in these hyperprolactinemic patients lends further support to a functional link between opioid and dopamine regulation of LH secretion.

Topics: Adenoma; Adult; Dopamine Antagonists; Female; Humans; Hyperprolactinemia; Luteinizing Hormone; Metoclopramide; Naloxone; Pituitary Neoplasms; Prolactin

With the aim of examining central opioid influences on the control of luteinizing hormone (LH) secretion, we evaluated the LH response to naloxone, an opioid receptor antagonist, in patients affected by normo-, hyper-, and hypogonadotropic amenorrhea, polycystic ovarian disease and hyperprolactinemia. The results indicate that opioid influences are altered in well-defined pathologic conditions (hyperprolactinemia, obesity), in addition to being modified by gonadal steroids.

Topics: Adenoma; Adolescent; Adult; Amenorrhea; Body Weight; Female; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Menstruation Disturbances; Naloxone; Oligomenorrhea; Ovary; Pituitary Neoplasms; Prolactin

Cells of the 7315c tumor released immunoreactive PRL (IR-PRL). Cholera toxin enhanced this release. Morphine and other opiate agonists inhibited IR-PRL release from both untreated and cholera toxin-treated tumor cells. The opiate-induced inhibition of IR-PRL release was concentration dependent and naloxone sensitive. Cholera toxin also enhanced the adenylate cyclase activity of 7315c tumor tissue. Opiates inhibited enzyme activity in both untreated and cholera toxin-treated 7315c tissue in a concentration-dependent and naloxone-sensitive manner. FK 33824 was more potent than [D-Ala2,D-Leu5]enkephalin in inhibiting IR-PRL release and adenylate cyclase activity. In cholera toxin-treated 7315c tumor tissue, GTP was required for opiate-induced inhibition of adenylate cyclase activity. Nonhydrolyzable analogs of GTP inhibited toxin-stimulated cyclase activity in the absence of an opiate. These results suggest that the 7315c tumor possesses a mu-opiate receptor; stimulation of this receptor inhibits both IR-PRL release and adenylate cyclase activity. An inhibitory guanyl nucleotide component may link the mu-opiate receptor to adenylate cyclase.

Topics: Adenylyl Cyclases; Animals; Cell Line; Cholera Toxin; Female; Guanosine Triphosphate; Kinetics; Morphine; Naloxone; Narcotic Antagonists; Pituitary Neoplasms; Prolactin; Rats; Rats, Inbred BUF; Receptors, Opioid; Receptors, Opioid, mu

Topics: Acromegaly; Addison Disease; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Lipotropin; Diethylstilbestrol; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Nelson Syndrome; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prolactin

ACTH excretion by cultured nonenzymatically dispersed pituitary tumor cells from a patient with Nelson's syndrome was studied. Hormone release was suppressed by 74 +/- 6% by the addition of 1 microM of the met-enkephalin analog FK 33824, while naloxone (1 microM) stimulated ACTH release by 70 +/- 5%. Somatostatin, dexamethasone, bromocriptine, and cyproheptadine in a concentration of 1 microM each inhibited ACTH release by 25 +/- 2%, 35 +/- 2%, 52 +/- 2%, and 61 +/- 4%, respectively, while lysine vasopressin (0.1 microM) and dibutyryl cAMP (5 mM) stimulated ACTH release by 112 +/- 8% and 220 +/- 4%, respectively. In conclusion, it was shown that the stimuli mentioned above directly affect ACTH secretion by the pituitary tumor cells. The inhibitory action of the met-enkephalin analog and the stimulatory action of naloxone on ACTH secretion make the presence of opiate receptors on this type of tumor likely.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cells, Cultured; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalins; Female; Hormones; Humans; Naloxone; Nelson Syndrome; Pituitary Neoplasms

Two patients with Nelson's syndrome and one patient after bilateral adrenalectomy for Cushing's disease, without any evidence of Nelson's syndrome, were studied with respect to the effect of hydrocortisone, naloxone and valproic acid (a GABA transaminase inhibitor) on ACTH secretion. Hydrocortisone suppressed plasma ACTH concentrations to normal in the patient without Nelson's syndrome, but failed to do so in the two patients with Nelson's syndrome. Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelson's syndrome, but produced no change in the patient without Nelson's syndrome. Secretion of ACTH may thus be influenced by both opiate peptide and by gamma aminobutyric acid, as well as by the cortisol concentration, these agents may act at different sites to inhibit ACTH release by the tumour.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Humans; Hydrocortisone; Middle Aged; Naloxone; Nelson Syndrome; Pituitary Neoplasms; Valproic Acid

In this study the effects of the implantation of the transplantable rat prolactin (PRL)-secreting pituitary tumor 7315a on gonadotropin secretion were investigated. Hyperprolactinemia was accompanied by suppressed plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The total PRL content of the host's pituitary gland was decreased, but the glands of tumor-bearing animals contained greatly increased amounts of LH and FSH. Chronic administration of naloxone to tumor-bearing rats for 5 days further diminished the already suppressed total PRL content of the pituitary gland, normalized the total LH content, and did not affect the FSH content. The pituitary glands from tumor-bearing rats given naloxone showed a higher ability to release LH in vitro. Hyperprolactinemia in rats is accompanied by an increased total gonadotropin content of the pituitary gland with lowered circulating gonadotropin levels. Some of the PRL-induced changes on LH synthesis and release are mediated by opioid receptors in the hypothalamus, as naloxone administration reversed some of these effects.

Topics: Animals; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Naloxone; Neoplasm Transplantation; Neoplasms, Experimental; Pituitary Neoplasms; Prolactin; Rats

This study assessed the effect of the opiate antagonist naloxone on anterior pituitary hormone release in normal subjects and patients with disturbances of the gonadotropic axis. Intravenous bolus injections of naloxone resulted in a rise of plasma LH, but had no significant effect on plasma levels of FSH or PRL. It also failed to alter the LH, FSH, or TSH response to LRF and TRH, although it did augment the PRL response to TRH. Slow iv infusion of naloxone resulted in increased plasma LH and FSH concentrations in both normal subjects and patients with hyperprolactinemia. The rise of LH correlated with the mean basal LH concentrations; a low basal level only responded to naloxone with a small increase in circulating LH concentration and vice versa. This relationship of the response of LH to the resting levels also held in several other pathological states in which there were marked differences of androgen and estrogen status as well as up to a 100-fold variation in basal LH concentrations. It is concluded that LH is under inhibitory opioid control both in normal subjects and in widely differing pathological states of the gonadotropic axis.

Topics: Adenoma; Adult; Craniopharyngioma; Female; Follicle Stimulating Hormone; Humans; Hypothyroidism; Luteinizing Hormone; Male; Naloxone; Pituitary Neoplasms; Polycystic Ovary Syndrome; Prolactin

Topics: Adenoma; Adult; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Kinetics; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin

The inhibiting role of endogenous opioid peptides on gonadotropin secretion was evaluated by the infusion of an opioid receptor antagonist, naloxone (1.6 mg/h for 4 h), in 10 hyperprolactinemic patients with pituitary microadenoma (prolactinoma) and 5 normal women during the early follicular phase of the cycle. In normal women, naloxone infusion induced no significant changes in any of the three pituitary hormones measured. Six prolactinoma patients with low normal levels of basal LH [10.0 +/- 1.0 mIU/ml +/- SE)] responded to naloxone infusion with an increment of circulating LH in the form of an amplified pulsatile pattern of release, which lasted for at least 2 h after the infusion. The other 4 patients with prepubertal levels of LH (4.9 +/- 0.8 mIU/ml) exhibited no LH response to naloxone. There were no significant changes in FSH or PRL levels in either group of patients. These findings suggest that an increased endogenous opioid inhibition of LH release occurs in patients with PRL-producing microadenoma.

Topics: Adenoma; Adult; Endorphins; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Luteinizing Hormone; Naloxone; Pituitary Neoplasms; Prolactin

Topics: Animals; Bromocriptine; Chorionic Gonadotropin; Erectile Dysfunction; Female; Humans; Hypogonadism; Libido; Luteinizing Hormone; Male; Naloxone; Pituitary Neoplasms; Prolactin; Rats; Testosterone

Clonal mouse pituitary tumor cells, AtT-20, synthesize at least four species of peptides with opiate activity. The endorphin concentration of AtT-20 cells was estimated to be 300-600 pmol/mg of protein. The two most abundant endorphins with apparent molecular weights of 1800 and 2400 were purified 300- and 24-fold, respectively; additional minor components were found with apparent molecular weights of greater than 3000 and less than 750.

Topics: Adenylyl Cyclases; Animals; Biological Assay; Cell Line; Clone Cells; Electric Stimulation; Endorphins; Enkephalins; Enzyme Activation; Guinea Pigs; Ileum; Kinetics; Naloxone; Oligopeptides; Peptide Biosynthesis; Peptide Hydrolases; Pituitary Neoplasms; Prostaglandins E