Endogenous Opiates Modulate Pulsatile Luteinizing Hormone Release in Humans*

Ropert, J.F.; Quigley, M. E.; Yen, S. S. C.

doi:10.1210/jcem-52-3-583

Cited by 255 publications

(86 citation statements)

References 26 publications

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“…This observation has been con firmed in rats and man [4,7,10,12,17]. We suggested that endogenous opioid peptides may tonically depress LH re lease during basal conditions [9].…”

supporting

confidence: 59%

Counteraction of Gonadal Steroid Inhibition of Luteinizing Hormone Release by Naloxone

et al. 1982

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The effect of naloxone on the negative feedback action of gonadal steroids on luteinizing hormone (LH) release was studied in castrated male and female rats. The reduction by estradiol benzoate or testosterone propionate of elevated serum LH levels in rats ovariectomized for 4 weeks was reversed by a single injection of naloxone. Injection of estradiol benzoate, together with progesterone, similarly reduced serum LH levels in ovariectomized rats, and this inhibition was partially reversed by naloxone. A single injection of testosterone propionate decreased serum LH levels in male rats castrated 48 h earlier, and naloxone completely blocked the androgen-induced inhibition of LH secretion. Chronic administration of either testosterone propionate or morphine sulfate to castrated male rats prevented the postcastration rise of serum LH. The decrease of hypothalamic LHRH in castrated rats was completely blocked by testosterone propionate or morphine sulfate administration. These results are believed to indicate that hypothalamic opiates are involved in gonadal steroid feedback inhibition of LH release.

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“…This observation has been con firmed in rats and man [4,7,10,12,17]. We suggested that endogenous opioid peptides may tonically depress LH re lease during basal conditions [9].…”

supporting

confidence: 59%

Counteraction of Gonadal Steroid Inhibition of Luteinizing Hormone Release by Naloxone

et al. 1982

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“…These naloxone doses, and the method of administration, were chosen based on previous experiments showing their effectiveness in modulating pulsatile LH secretion in humans and female mon keys. The dose of 0.5 mg/h was chosen because this dose was simi lar to naloxone doses (0.03-0.06 m g/kg/h) that had been shown to increase LH pulse frequency in men and women in a variety of physiological conditions [16][17][18][19], The dose of 2.0 mg/h had been shown to increase LH pulse frequency during the luteal phase in rhesus monkeys [20,21], and the doses of 2.0 and 5.0 mg/h have been shown to reverse the effects of CRH on LH secretion in ovariectomized rhesus monkeys [22[. In this preliminary study, the dose of 2.0 mg/h produced the most consistent and sustained elevation in LH pulse frequency.…”

Section: Methodsmentioning

confidence: 99%

Suppression of Luteinizing Hormone Secretion during Food Restriction in Male Rhesus Monkeys (<i>Macaca mulatta</i>): Failure of Naloxone to Restore Normal Pulsatility

Helmreich¹,

Cameron²

1992

Neuroendocrinology

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Short periods of fasting have been shown to cause a significant slowing of pulsatile LH secretion in men and male rhesus monkeys, which appears to result from a slowing of GnRH drive to the reproductive axis. To determine whether an increased activity of endogenous opioid peptides causes this slowing of pulsatile LH secretion, the ability of naloxone administration to reverse the fasting-induced suppression of LH secretion was tested. For this study, 6 adult male rhesus monkeys, with indwelling femoral and jugular venous catheters, were maintained on tether/swivel systems. Naloxone was administered to monkeys as a continuous infusion (0.25 mg/kg/h, with an initial loading dose of approximately 1.0 mg) for 8 h (16.00 to 24.00 h) on a day of normal feeding and again on a day of fasting. The LH response to naloxone was determined by collecting blood samples every 15 min from 12.00 to 24.00 h. LH pulse frequency on a day of normal feeding was 4.0 ± 0.52 pulses/8 h, and naloxone administration on a day of feeding increased LH pulse frequency to 6.8 ± 0.86 pulses/8 h. On a day of fasting, LH pulse frequency was 1.67 ± 0.67 pulses/8 h, and naloxone administration on a day of fasting slightly, but not significantly, increased LH pulse frequency to 2.5 ± 0.51 pulses/8 h. Similar studies were performed with a higher dose of naloxone (0.625 mg/kg/ h, with an initial loading dose of approximately 2.0 mg) and again naloxone administration did not reverse the effects of fasting on pulsatile LH secretion. These results suggest that the slowing of pulsatile LH release that occurs with short periods of food restriction does not result from increased secretion of endogenous opioid peptides.

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“…Moreover, the administration of opiate-receptor antagonists alone significantly amplifies the pulsatile mode of LH release, with attendant increases in the frequency and peak amplitude ofboth immunoactive and biologically active LH pulses (1 1-15). The ability of opiate-receptor antagonists to enhance episodic LH secretion in vivo (11)(12)(13)(14)(15) and to stimulate gonadotropin-releasing hormone (GnRH) secretion from human hypothalamic tissue in vitro (16,17) has suggested that the inhibitory action of endogenous opiates is exerted at the level of the hypothalamic pulse generator for GnRH.…”

Section: Introductionmentioning

confidence: 99%

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Veldhuis¹,

Rogol²,

Samojlik³

et al. 1984

J. Clin. Invest.

193

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As bstract. We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation.When the pure (nonaromatizable) androgen, 5-a-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition ofLH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-1 7,3 did not change significantly, but serum 5a-dihydrotestosterone concentrations increased approximately two-to threefold, with a corresponding increase in levels of its major me- tabolite, 5a-androstan-3a, 17f-diol. In separate experiments, the infusion of estradiol-1 7#3 at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-1 73 levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions.Our observations indicate that, despite the continuous infusion of a dosage of 5a-dihydrotestosterone that significantly suppresses LH pulse frequency, co-administration of an opiate-receptor antagonist effectively reinstates LH pulse frequency to control levels. Moreover, during the infusion of a suppressive dose of estradiol-1 73, opiate receptor blockade significantly augments LH pulse frequency and increases LH peak amplitude to control levels.Thus, the present studies in normal men demonstrate for the first time that the selective inhibitory action of a pure androgen on LH pulse frequency is effectively antagonized by opiate-receptor blockade. This pivotal oW servation indicates that opiatergic and androgen-dependent mechanisms specifically and coordinately control the hypothalamic pulse generator for gonadotropin-re- We conclude that the negative feedback actions of gonadal steroids are integrally coupled to endogenous opiate pathways and that such functional coupling is ultimately expressed at least in part at the level of the hypothalamic pulse generator for GnRH. These observations suggest a model for the proximate regulation of gonadotropin secretion in man, in which the regulatory actions of two major inhibitory systems...

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Endogenous Opiates Modulate Pulsatile Luteinizing Hormone Release in Humans*

Cited by 255 publications

References 26 publications

Counteraction of Gonadal Steroid Inhibition of Luteinizing Hormone Release by Naloxone

Counteraction of Gonadal Steroid Inhibition of Luteinizing Hormone Release by Naloxone

Suppression of Luteinizing Hormone Secretion during Food Restriction in Male Rhesus Monkeys (<i>Macaca mulatta</i>): Failure of Naloxone to Restore Normal Pulsatility

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

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