Biomedical subjects

K T O'Byrne

Publications and source records attributed to K T O'Byrne.

At least 19 recordsLinked to original sources

PubMed2006

Differential role of corticotrophin-releasing factor receptor types 1 and 2 in stress-induced suppression of pulsatile luteinising hormone secretion in the female rat.

Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF(2)) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF(1)) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF(1) and CRF(2) in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 microl) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 microg/kg). All three stressors suppressed LH pulses. The CRF(1) antagonist SSR125543Q (11.5 micromol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF(2) antagonist astressin(2)-B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF(2) while restraint stress-induced inhibition of LH pulses involves both CRF(1) and CRF(2).

Animals↗

PubMed2005

Calcitonin gene-related peptide-induced suppression of luteinizing hormone pulses in the rat: the role of endogenous opioid peptides.

Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamo-pituitary-adrenal axis resulting in increased corticosterone secretion. We have previously shown that central CGRP suppresses the gonadotrophin-releasing hormone (GnRH) pulse generator, specifically LH pulses. Endogenous opioid peptides (EOPs) have been shown to play an important role in stress-induced suppression of the reproductive axis. The aim of the present study was to test the hypothesis that EOPs mediate CGRP-induced suppression of pulsatile LH secretion. Ovariectomized rats were implanted with intracerebroventricular (i.c.v.) and i.v. cannulae. Intravenous administration of the opioid antagonist naloxone (250 microg) completely blocked the suppression of LH pulses induced by 1.5 microg i.c.v. CGRP and significantly attenuated the suppression of pulsatile LH secretion induced by 5 microg i.c.v. CGRP. Furthermore, intravenous administration of naloxone was found to immediately restore normal LH pulse frequency in animals treated 90 min earlier with 1.5 microg i.c.v. CGRP. Co-administration (i.c.v.) of CGRP (1.5 microg) with the mu and kappa opioid receptor-specific antagonists naloxone (10 microg) and norbinaltorphimine (5 microg), respectively, blocked the CGRP-induced suppression of LH pulses, whilst i.c.v. co-administration of CGRP (1.5 microg) with the delta opioid receptor-specific antagonist naltrindole (5 microg) did not. These data provide evidence that EOPs play a pivotal role in mediating the inhibitory effects of CGRP on pulsatile LH secretion in the rat. They also suggest that the mu and kappa, but not the delta, opioid receptors may be responsible for mediating the effects of CGRP on LH pulses.

Animals↗

PubMed2005

Effect of calcitonin gene-related peptide on gonadotrophin-releasing hormone mRNA expression in GT1-7 cells.

Recent evidence has shown calcitonin gene-related peptide (CGRP) to be a key mediator of stress-induced suppression of the gonadotrophin-releasing hormone (GnRH) pulse generator, although little is known about the neural pathways involved. In the present study, we investigated the potential direct action of CGRP on GnRH neurones using GT1-7 cells, an established GnRH cell line. First, we detected expression of the CGRP receptor subunits, calcitonin receptor-like receptor and receptor activity-modifying protein-1 in the GT1-7 cells by reverse transcriptase-polymerase chain reaction. Second, we have shown that CGRP inhibits GnRH mRNA expression in the GT1-7 cells, which was effectively reversed by the CGRP receptor antagonist, CGRP8-37. These results suggest that CGRP down regulates expression of GnRH mRNA, via CGRP receptors in the GT1-7 cell, thus implying that a potential direct action of CGRP may mediate a suppressive effect on the GnRH neural network.

Calcitonin Gene-Related Peptide↗

PubMed2004

The role of the locus coeruleus in corticotropin-releasing hormone and stress-induced suppression of pulsatile luteinizing hormone secretion in the female rat.

Despite a wealth of evidence for CRH mediating stress-induced suppression of the hypothalamic GnRH pulse generator, and hence reproductive dysfunction, the site and mechanism of action remains elusive. The locus coeruleus (LC), a prominent noradrenergic brain stem nucleus, is innervated by CRH neurons, mediates several behavioral stress responses, and is implicated in the control of pulsatile LH secretion. The aim of this study was to test the hypothesis that LC CRH has a critical role in mediating stress-induced suppression of pulsatile LH secretion in the rat. Ovariectomized rats with 17beta-estradiol or oil-filled s.c. capsules were implanted with bilateral LC and i.v. cannulae. Central administration of CRH (10 ng to 1 microg) resulted in a dose-dependent suppression of LH pulses, which was reversed by a CRH receptor antagonist (alpha-helical CRF(9-41), 1 microg). The induction of c-fos expression in glutamic acid decarboxylase67 immunostained neurons in the preoptic area suggests activation of the secretion of gamma-aminobutyric acid in response to intracoerulear administration of CRH; 17beta-estradiol further increased the percentage of glutamic acid decarboxylase67-positive neurons that expressed fos and augmented suppression of LH pulses. Furthermore, intracoerulear administration of alpha-helical CRF(9-41) completely blocked restraint stress-induced suppression of LH pulses, without affecting the inhibitory response to hypoglycemia. These results suggest that CRH innervation of the LC may play a pivotal, but differential, role in the normal physiological response of stress-induced suppression of the GnRH pulse generator and hence the reproductive system.

Animals↗

PubMed2004

The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic stress-induced suppression of pulsatile LH secretion in the female rat.

Corticotrophin-releasing hormone (CRH) released during stress has been implicated in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol (E2) has been shown to enhance stress-induced suppression of pulsatile gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The aims of the present study were to examine the role of CRH in hypoglycaemic stress-induced suppression of LH pulses, and to investigate the influence of E2 on the inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely prevented by intracerebroventricular (icv) administration of a CRH antagonist. Central administration of CRH (5 microg) resulted in an interruption of LH pulses in E2 treated animals, but had little or no effect in the absence of this gonadal steroid. These results provide evidence of a pivotal role for CRH in mediating the suppressive effect of IIH stress on pulsatile LH secretion in the female rat, and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.

Animals↗

PubMed2004

Differential effects of repeated restraint stress on pulsatile lutenizing hormone secretion in female Fischer, Lewis and Wistar rats.

Stress activates the hypothalamic-pituitary-adrenocortical (HPA) axis and can suppress pulsatile luteinizing hormone (LH) secretion, resulting in reproductive dysfunction. The histocompatible inbred Fischer and Lewis rat strains exhibit marked phenotypic differences in the activity of the HPA axis, the former being more reactive. Using Fischer, Lewis and Wistar rats, we assessed effects of repeated restraint stress on pulsatile LH secretion. Adult rats were ovariectomized and fitted with cardiac catheters. Blood samples were collected at 5-min intervals for 3-5 h for detection of LH. Less frequent samples were collected for corticosterone measurement. After 2 h, rats were restrained for 60 min. The same regimen was repeated four times at 6-day intervals. The mean peak corticosterone levels achieved during the first restraint in Fischer rats were significantly higher than those in Lewis and Wistar rats. By the time of the fourth episode of restraint, there had been some adaptation of the corticosterone response in the Fischer, but not in the Lewis or Wistar rats. LH pulses were interrupted during the 1st restraint in all experimental groups, although only Fischer rats showed suppression of LH pulses during the subsequent 2-h postrestraint period. During the fourth restraint, LH pulse frequency was still reduced in Wistar, but not in Fischer and Lewis rats, both of which showed a complete habituation. These results suggest that differential control mechanisms underlie the response of the HPA and HPG axes to repeated restraint stress.

Adaptation, Physiological↗

PubMed2003

The effects of the phytoestrogen, coumestrol, on gonadotropin-releasing hormone (GnRH) mRNA expression in GT1-7 GnRH neurones.

Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans, although little is known about the mechanisms and the role of direct action on oestrogen receptors (ER) in this process. We examined the effect of coumestrol, alone and combined with ER antagonists, on gonadotropin-releasing hormone (GnRH) mRNA expression in GT1-7 cells. Coumestrol was found to have an inhibitory effect compared to controls, which was blocked by R,R-THC, a selective ER beta antagonist. These results suggest that ER beta is involved in the suppression of GnRH mRNA expression by coumestrol.

Cell Line↗

PubMed2003

The effect of oestradiol and progesterone on hypoglycaemic stress-induced suppression of pulsatile luteinizing hormone release and on corticotropin-releasing hormone mRNA expression in the rat.

Corticotropin-releasing hormone (CRH) is implicated in the suppression of pulsatile luteinizing hormone (LH) secretion by a variety of stressful stimuli; 17beta-oestradiol (E2) has been shown to modulate this inhibitory response. The present study in ovariectomized (OVX) rats was designed to investigate the effect of E2 and progesterone (P4) on hypoglycaemic stress-induced changes in pulsatile LH secretion and on the associated changes in both central and peripheral components of the hypothalamic-pituitary-adrenal axis. E2 enhanced the hypoglycaemic stress-induced suppression of LH pulses; P4 in addition to E2 further potentiated the inhibitory response. The rise in plasma corticosterone following insulin-induced hypoglycaemia (IIH) was highest in the E2 + P4 group. Nevertheless, when such levels were achieved by administration of corticosterone, the occurrence of LH pulses was completely unaffected, irrespective of ovarian steroid milieu. E2 and E2 + P4 up-regulated basal CRH mRNA expression in the paraventricular nucleus (PVN) as measured by in situ hybridization; this signal was also increased in the medial preoptic nucleus (MPN) following E2. IIH resulted in a rise in CRH mRNA in the PVN, but not in the MPN; this rise may reflect a more significant role for the PVN in the present context. Changes in neuropeptide mRNA expression may signal changes in neuronal activity; nevertheless, the profound differences in LH pulse suppression in OVX, E2 and E2 + P4 rats following IIH were not reflected in the concurrent changes in CRH mRNA in the PVN. The results suggest that while corticosterone has no acute effect on LH pulses in the rat, the up-regulation by ovarian steroids of basal CRH mRNA in the PVN and/or MPN may contribute to the central regulation of these pulses in response to stress.

Adrenocorticotropic Hormone↗

PubMed2001

Phytoestrogens and gonadotropin-releasing hormone pulse generator activity and pituitary luteinizing hormone release in the rat.

Phytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans. The aims of this study were 2-fold: 1) to determine in vivo whether genistein and coumestrol act on the GnRH pulse generator to suppress hypothalamic multiunit electrical activity volleys and associated LH pulses and/or on the pituitary to suppress the LH response to GnRH; and 2) to examine the effect of these phytoestrogens on GnRH-induced pituitary LH release in vitro and to determine whether estrogen receptors are involved. Wistar rats were ovariectomized and chronically implanted with recording electrodes and/or indwelling cardiac catheters, and blood samples were taken every 5 min for 7--11 h. Intravenous infusion of coumestrol (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) resulted in a profound inhibition of pulsatile LH secretion, a 50% reduction in the frequency of hypothalamic multiunit electrical activity volleys, and a complete suppression of the LH response to exogenous GnRH. In contrast, both genistein (1.6-mg bolus followed by 2.4 mg/h for 8.5 h) and vehicle were without effect on pulsatile LH secretion. Coumestrol (10(-5) M; over 2 or 4 h) suppressed GnRH-induced pituitary LH release in vitro, an effect blocked by the antiestrogen ICI 182,780. It is concluded that coumestrol acts centrally to reduce the frequency of the hypothalamic GnRH pulse generator. In addition, the inhibitory effects of coumestrol on LH pulses occur at the level of the pituitary by reducing responsiveness to GnRH via an estrogen receptor-mediated process.

Animals↗

PubMed2000

The area postrema mediates insulin hypoglycaemia-induced suppression of pulsatile LH secretion in the female rat.

The caudal brainstem has been implicated in mediating the suppressive effect of glucoprivation on the reproductive neuroendocrine axis, specifically inhibition of pulsatile gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) release in the rat. In the present study, removal of the area postrema completely prevented the profound inhibitory effect of insulin-induced hypoglycaemic stress on pulsatile LH release. These results suggest a pivotal role for this brainstem structure in mediating hypoglycaemic stress-induced suppression of the hypothalamic GnRH pulse generator.

Animals↗

PubMed1999

Ketamine-induced general anesthesia is compatible with gonadotropin-releasing hormone pulse generator activity in gonadectomized rats: prospects for detailed electrophysiological studies in vivo.

Previous studies on the mediobasal hypothalamus (MBH) of rats, rhesus monkeys and goats have detected episodic increases in multiunit activity (MUA volleys) which immediately precede a pulse of luteinizing hormone (LH). These volleys are considered to reflect the activity of the gonadotropin-releasing hormone (GnRH) pulse generator. Our understanding of this system would be greatly enhanced if it were possible to study the electrophysiological aspects of this system at the single cell level; such an approach requires anesthesia of the animals (as in the classic studies on the oxytocin and vasopressin systems). Although it is widely held that anesthetic agents disrupt the processes regulating LH release, little is known about their specific effects on the dynamics of this system. Using on-line electrophysiological techniques in addition to subsequent radioimmunoassay for LH, we have found that anesthesia by ketamine is compatible with the continued production of MUA volleys and LH pulses in gonadectomized rats. In contrast to the hypothermia induced by the LH pulse-suppressing anesthetic sodium pentobarbitone, a small rise in core temperature occurs following ketamine. The present findings offer the prospect of detailed electrophysiological analysis of GnRH pulse generator activity in rats maintained under general anesthesia.

Anesthesia, General↗

PubMed1998

Relaxin inhibits the pulsatile release of oxytocin but increases basal concentrations of hormone in lactating rats.

The effects of porcine relaxin were examined in urethane-anesthetized, lactating rats to clarify the actions of relaxin on basal levels and the pulsatile release of oxytocin during suckling. Baseline plasma oxytocin concentrations were 27.6+/-2.9 pM in unsuckled rats. They were significantly increased in rats after the onset of suckling (34.5+/-2.4 pM) compared with unsuckled animals. Oxytocin concentrations were increased further during reflex milk ejection (41.2+/-2.7 pM). Treatment with porcine relaxin (5 microg in 0.1 ml saline) caused a significant (p < 0.05) increase in plasma oxytocin compared with pretreatment concentrations or saline injection in all three groups. Frequent blood samples were taken before and during milk ejection to confirm pulsatile oxytocin associated with reflex milk ejection. Short-lived (5-10-sec) pulses with peak concentrations of oxytocin 392.4+/-122.1 pM were observed shortly before or at the time of the peak rise in intramammary pressure associated with reflex milk ejection. Relaxin (5 microg i.v.) completely suppressed the pulsatile release of oxytocin. These data suggest that relaxin increases basal secretion of oxytocin but inhibits the pulsatile secretion associated with reflex milk ejection.

Animals↗

PubMed1998

On the mechanism of lactational anovulation in the rhesus monkey.

The relative roles of infant suckling and of maternal prolactin (PRL) secretion in lactational anovulation were studied in ovary-intact and ovariectomized rhesus monkeys nursing young that had been removed from their natural mothers. Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was monitored electrophysiologically in freely behaving animals by radiotelemetry. Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured. Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all ovary-intact females but had no such effect on the pulse generator in long-term ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine administration, GnRH pulse generator activity remained significantly inhibited and ovulation was prevented in four monkeys (6 trials), whereas in two females (6 trials) a rapid increase in pulse generator frequency and the resumption of ovarian cyclicity were observed although suckling activity was maintained. One monkey displayed both response types. Although these results indicate that suckling per se is able to restrain GnRH pulse generator activity in the absence of PRL, they also suggest that the relative importance of these determinants is variable depending on factors that remain to be determined. The present study also confirms the permissive role of the ovary in the lactational suppression of GnRH pulse generator activity.

Animals↗

PubMed1997

Hypoglycaemia-induced inhibition of pulsatile luteinizing hormone secretion in female rats: role of oestradiol, endogenous opioids and the adrenal medulla.

Oestradiol (E2) has been shown to exacerbate the inhibitory effect of hypoglycaemic stress on gonadotrophin-releasing hormone pulse generator (GnRH) activity in primates. The mechanism by which this is mediated is not yet known. We therefore aimed to establish whether there is a sensitizing influence of E2 on the suppression of LH pulsatility in response to hypoglycaemia in the female rat, thus providing a more amenable model in which to study this phenomenon. In ovariectomized Wistar rats with E2 replacement, insulin-induced hypoglycaemia (0.5 U/kg i.v.) resulted in an interruption of pulsatile LH secretion. Induction of the same degree of hypoglycaemia in ovariectomized rats without E2 replacement was without effect on LH pulsatility. Naloxone administration prevented the hypoglycaemia-induced inhibition of LH pulses. Because hypoglycaemia is a potent activator of the sympathetic nervous system, we also tested the hypothesis that the adrenal medulla is involved in this suppression of LH pulses in the rat. Adrenomedullectomy completely prevented this inhibitory response to hypoglycaemic stress. These data are consistent with the hypothesis that E2 sensitizes the GnRH pulse generator to the inhibitory influences of hypoglycaemic stress in the rat. Furthermore, a clear role for both endogenous opioid peptides and the adrenal medulla in the stress-induced suppression of LH pulsatility is identified.

Adrenal Medulla↗

PubMed1996

The insulin hypoglycemia-induced inhibition of gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: roles of vasopressin and corticotropin-releasing factor.

Insulin-induced hypoglycemia (IIH) profoundly inhibits the activity of the hypothalamic GnRH pulse generator. The aim of this study was to determine the role of vasopressin and CRF in this response. Ovariectomized rhesus monkeys with chronically implanted recording electrodes in the mediobasal hypothalamus and with intracerebroventricular (icv) cannulas in the lateral ventricle were placed in primate chairs, and blood samples were taken every 10 min. Pulse generator activity was monitored electrophysiologically by detecting characteristic increases in hypothalamic multi-unit activity (MUA volleys) and by attendant LH pulses measured in peripheral blood. Arginine vasopressin (AVP) infused via the i.c.v. cannula (50 micrograms/60 microliters.h) in eight monkeys failed to decrease pulse generator activity, as measured by the frequency of MUA volleys, but decreased mean serum LH concentrations (P < 0.001) while increasing serum cortisol levels (P < 0.02). Central administration of an AVP antagonist ([deamino-Pen1, O-Me-Tyr2-Arg8] vasopressin) in four monkeys at a rate (180 micrograms/60 microliters.h) that had previously been found to block the aforementioned effects of coadministered AVP failed to prevent the IIH-induced inhibition of GnRH pulse generator activity and LH secretion in the same animals. On the other hand, a CRF antagonist, [D-Phe12,Nle21,38,C alpha MeLeu37] rat CRF-(12-41), infused i.c.v. at a rate of 500 micrograms/60 microliters.h in four monkeys, delayed the inhibition of pulse generator frequency in response to IIH. These results suggest that AVP does not mediate the hypoglycemia-induced inhibition of GnRH pulse generator frequency in the rhesus monkey, but that CRF may be involved in this response.

Animals↗

PubMed1993

Single unit components of the hypothalamic multiunit electrical activity associated with the central signal generator that directs the pulsatile secretion of gonadotropic hormones.

Vertebrate reproduction is dependent on the operation of a central signal generator that directs the episodic release of gonadotropin-releasing hormone, a neuropeptide that stimulates secretion of the pituitary gonadotropic hormones and, thereby, controls gonadal function. The electrophysiological correlates of this pulse generator are characterized by abrupt increases in hypothalamic multiunit electrical activity (MUA volleys) invariably associated with the initiation of secretory episodes of luteinizing hormone. Using cluster analysis, we extracted single units from the multiunit signals recorded from the mediobasal hypothalamus of four intact and four ovariectomized rhesus monkeys. Of the 40 individual units identified in this manner, 24 increased their frequency with the MUA volleys. The onset and termination of these single-unit bursts occurred coincidently with those of the MUA volleys in both intact and ovariectomized animals, indicating that the longer duration of the MUA volleys characteristic of the gonadectomized animals was due not to the sequential activation of different units but to the longer bursts of the individual cells. Four other units showed decreases in firing rate during the MUA volleys, while the frequency of the remainder did not change. All the examined units were active during the intervals between the volleys of electrical activity. The results indicate that the MUA volleys associated with the activity of the gonadotropin-releasing hormone pulse generator represent the simultaneous increase in firing rate of some individual hypothalamic neurons and the decrease in the frequency of others.

Action Potentials↗

PubMed1993

Electrophysiological approaches to gonadotrophin releasing hormone pulse generator activity in the rhesus monkey.

Precipitous increases in multi-unit electrical activity (MUA volleys) can be recorded from the mediobasal hypothalamus of the rhesus monkey that are invariably synchronous with the initiation of luteinizing hormone (LH) pulses and thus serve as markers of gonadotrophin releasing hormone (GnRH) pulse generator activity. Continuous radiotelemetric monitoring of this activity throughout the menstrual cycle confirmed a lower pulse generator frequency during the luteal phase than in the follicular phase. Unexpectedly, however, just before the initiation of the LH surge an abrupt reduction in frequency was observed, followed, on occasion, by a total arrest of GnRH pulse generator activity for a day or two. This monitoring technique also revealed a reduction of pulse generator frequency at night. This appeared to be an acute phenomenon observable in the first MUA volleys after the lights are turned off, as is the increase in frequency when the lights are turned on in the morning suggesting a direct action of light, a conclusion that was verified using lighting periods other than the customary ones. This action of light, however, is superimposed upon a diurnal rhythm, as shown by a reduction in pulse generator frequency during the subjective night when the monkeys are kept in constant light or darkness. The duration of the MUA volley in the intact monkey is 1-3 min, compared with some 20 min in the ovariectomized female. While oestradiol reduces the volley duration in the ovariectomized female to that of intact monkeys within 6 h, it takes some 6 weeks following ovariectomy for the duration characteristic of castrates to be re-established.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of naloxone on estrogen-induced changes in hypothalamic gonadotropin-releasing hormone pulse generator activity in the rhesus monkey.

In the ovariectomized rhesus monkey, estradiol (E2) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E2 was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E2 levels achieved by subcutaneous implantation of E2-containing Silastic capsules increased MUA volley interval from 50.8 +/- (SEM) 1.6 min in the control period to 81.1 +/- 6.2 min following E2. Mean MUA volley duration decreased from 21.9 +/- 1.0 to 13.0 +/- 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E2 on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E2 on MUA volley duration, (13.0 +/- 0.7 vs. 14.0 +/- 0.9 min). These findings suggest that the inhibitory action of E2 on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗