Naloxone-induced secretion of LH in the male Syrian hamster: modulation by photoperiod and gonadal steroids

The role of endogenous opiates in the regulation of photoperiodically induced testicular regression was studied in the male Syrian hamster. In reproductively active hamsters exposed to a long photoperiod (LD; 16 h light: 8 h darkness) or to short days (SD; 8 h light: 16 h darkness) for 20 weeks or to SD after pinealectomy, administration of naloxone, a competitive opiate receptor antagonist, at doses of 2.5-20 mg/kg, significantly increased serum LH concentrations. In marked contrast, these doses of naloxone did not produce any change in LH levels in reproductively quiescent hamsters exposed to SD for 8 weeks. The influence of gonadal steroids on the LH response to naloxone was studied in hamsters castrated or castrated and implanted s.c with a capsule containing testosterone. Naloxone did not induce LH release in castrated hamsters maintained in LD or in SD, but this response was restored in LD but not SD when serum testosterone concentrations were maintained at levels similar to those observed in intact reproductively active hamsters. These results show that inhibition of reproduction by the photoperiod prevents naloxone-induced LH release in the male hamster. This lack of response to naloxone is not due, however, to the lower testosterone titres present in these animals compared with reproductively active animals. Responsiveness to naloxone can be restored when the animal is rendered insensitive to the inhibitory photoperiod either by removal of the pineal gland or by induction of photorefractoriness by extended exposure to SD.     

Endogenous opioids and the control of seasonal LH secretion in Soay rams

Soay rams were treated with naloxone and/or morphine at different stages of their annual reproductive cycle to study the role of endogenous opioid peptides in the control of pulsatile LH secretion. The responses in intact rams were compared with those shown by pinealectomized (PNX) or superior cervical ganglionectomized (SCGX) rams which had a different annual testicular cycle. Naloxone (4-6 mg/kg i.v.) given to intact rams at four times of the year induced significant increases in LH pulse frequency in the breeding season in September and December, but minimal responses in the non-breeding season in June. Similar treatments given to PNX or SCGX rams induced good responses in March, June and September and the poorest response in December; the different seasonal pattern between the intact and PNX/SCGX rams was correlated with differences in the timing of their testicular cycles. Morphine (1 mg/kg i.v.) induced a significant decrease in LH pulse frequency when given to intact rams in October, but no significant effects were observed when morphine was given to sexually inactive rams in early July. Naloxone (1 mg/kg i.v.) given concurrently with morphine in October reversed the suppressive effect and resulted in an actual increase in LH pulse frequency above pretreatment levels. Morphine-treated rams showed normal LH responses to injections of LH-releasing hormone (LHRH) indicating that the site of opiate inhibition was on hypothalamic LHRH secretion rather than on pituitary LH release. Chronic treatment of intact and PNX rams with naloxone (1 mg/kg every 4 h for 7 days) in April and October produced the expected acute increase in LH pulse frequency in the intact rams in October, and at both times of year in the PNX rams, however there was no sustained increase in LH secretion in response to chronic naloxone in any of the treatment groups. The response to the second naloxone injection was much reduced and was absent after 3 days; responsiveness to naloxone was restored within 2 days of stopping the chronic treatment. The overall results indicate that endogenous opioid mechanism is involved in the tonic inhibition of LH secretion and that this mechanism is most active in the breeding season when both naloxone and morphine have marked effects on pulsatile release of LH. Regulation of endogenous opioids in the hypothalamus may be part of the mechanism by which environmental factors modulate steroid negative-feedback control of LHRH and thus LH secretion in seasonally breeding mammals.     

Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine

Evidence from several species suggest that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33-824 (0.5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33-824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33-824 or FK 33-824 plus naloxone. That FK 33-824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33-824 (1 mumol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous opioid modulation of pancreatic hormone secretion: studies in dogs

The role of endogenous opioid peptides in the modulation of secretion of hormones from the endocrine pancreas was studied in dogs. In response to insulin-induced hypoglycemia, plasma glucagon secretion significantly increased, followed by an increase in plasma somatostatin immunoreactivity. Pretreatment with the opiate antagonist, naloxone, prevented the somatostatin response but had no effect on the augmented glucagon secretion. Neither the degree of hypoglycemia nor recovery from the induced glucose nadir were affected by naloxone. Arginine Hcl administration resulted in prompt increases in immunoreactive glucagon and insulin secretion, as well as a rise in serum glucose. Pretreatment with naloxone failed to affect any of these responses. Our results suggest that endogenous opioid peptides mediate the somatostatin response following hypoglycemia-induced glucagon secretion.     

Beta-endorphin secretion in rams related to season and photoperiod

A newly established RIA was used to measure changes in the concentration of beta-endorphin in peripheral blood and pituitary tissue from adult Soay rams living outside under natural conditions and housed indoors under artificial photoperiods. A pronounced seasonal cycle in plasma beta-endorphin immunoreactivity occurred in the outdoor animals, with low levels in spring and early summer (February-May; less than 200 pg/ml plasma) and maximal levels 10-20 times higher in late summer and autumn (July-October). Seasonal changes in plasma levels of PRL, FSH, and cortisol, testis size, and body weight were also monitored; the seasonal cycle in the levels of immunoreactive beta-endorphin occurred in parallel with the cycle in plasma FSH and body weight. There were no significant seasonal changes in plasma cortisol concentrations. Marked changes in the plasma levels of beta-endorphin were also seen in rams kept under the artificial photoperiod regimen of alternating 12- to 16-week periods of long days (16 h of light and 8 h of darkness; 16L:8D) and short days (8L:16D). Transfer from long days to short days led to a greater than 20-fold increase in the levels of beta-endorphin, reaching a maximum after 4-8 weeks; the reverse switch in photoperiod led to a rapid decrease in the levels. There was no diurnal rhythm in the plasma levels of beta-endorphin based on hourly samples collected for 24 h under long and short days. The total content of immunoreactive beta-endorphin in the pituitary gland was lower in rams under short days than under long days, converse to the pattern in the blood. Sephadex chromatography of the plasma samples revealed that most of the beta-endorphin immunoreactivity coeluted with synthetic beta-endorphin-(1-31), and a small amount of activity eluted with beta-lipotropin. The seasonal and photoperiod-induced changes were largely due to changes in the levels of beta-endorphin. Extracts of pituitary tissue revealed a large proportion of beta-lipotropin to beta-endorphin compared to plasma, with no consistent change in ratio related to the photoperiod. The overall results illustrate that there are pronounced seasonal and photoperiod-induced changes in immunoreactive plasma beta-endorphin levels in the ram. Under artificial photoperiods, long days inhibit and short days stimulate beta-endorphin secretion. Under natural conditions, the development of refractoriness to both the inhibitory effects of long days and the stimulatory effects of short days may explain the timing of the annual cycle of beta-endorphin secretion.     

Endogenous opioid peptide regulation of pulsatile luteinizing hormone secretion during pregnancy in the rat

The objective of this study was to determine if endogenous opioid peptides (EOPs) influence the pattern of pulsatile luteinizing hormone (LH) secretion on days 6-8, 14-16 and 22 of gestation in the rat. Unanesthetized animals with two jugular cannulae were initially infused with 0.9% saline during which the control pattern of pulsatile LH release was determined. Possible EOP involvement was then determined by infusion of the EOP receptor antagonist naloxone. Plasma estradiol (E2) and progesterone (P) values increased between days 6-8 and 14-16. While plasma E2 values remained elevated through day 22, plasma P values declined by 90%. As previously reported, mean blood LH levels during the control period on day 22 were higher than on days 6-8 and 14-16 due to an increase in LH pulse frequency. At each stage of gestation naloxone infusion increased mean blood LH levels. This stimulatory action of naloxone was reduced in a dose-dependent fashion by simultaneous infusion with morphine, demonstrating that this effect is mediated via EOP receptors. There was no difference in the in vivo pituitary responsiveness to LH-releasing hormone (LHRH) between rats infused with saline or naloxone at any stage of pregnancy, demonstrating that the stimulatory effect of naloxone was not exerted at the pituitary level. Naloxone increased both the amplitude and frequency of pulsatile LH secretion on days 6-8, and stimulated frequency on days 14-16. The effect on amplitude could not be assessed on days 14-16 because too few rats exhibited pulsatile LH secretion prior to naloxone infusion. The increase in pulse frequency was similar on days 6-8 and 14-16. Although naloxone increased LH pulse amplitude and frequency on day 22, these increases were significantly less than those seen on days 6-8 and 14-16, respectively. Pituitary responsiveness to LHRH was less at all stages of pregnancy in comparison to responsiveness in ovariectomized rats, and progressively declined from days 6-8 through day 22. The lowest responsiveness to LHRH was seen on day 22 and contributed, at least in part, to the diminished increase in LH pulse amplitude in response to naloxone infusion on day 22 compared to days 6-8. The reduced naloxone-induced increment in LH pulse frequency on day 22, occurring coincident with a precipitous decline in plasma P levels, suggests a decreased EOP suppression of pulse frequency at this time.(ABSTRACT TRUNCATED AT 400 WORDS)     

A comparison of the effects of gonadal steroids on naloxone-induced LH secretion in gonadectomized rats

The effects of the opiate antagonist naloxone on serum LH concentrations was investigated in gonadectomized rats given different regimes of steroid pretreatment. Two injections of testosterone given 48 and 24 h before naloxone treatment failed to reinstate LH responses to this drug in castrated rats while subcutaneous testosterone-filled silicone elastomer capsules implanted for a week were effective in this respect. Injections of oestrogen, oestrogen plus progesterone or progesterone alone all restored LH responses to naloxone in ovariectomized rats when given 48 and/or 24 h before drug treatment, although the magnitude of these responses varied according to the precise steroid treatments. The hypothalamic-pituitary axis was also responsive to naloxone just before the progesterone-induced LH surge in oestrogen-primed ovariectomized rats. Results show that gonadal steroids are permissive to the effects of opiate drugs, but they suggest that endogenous opioid systems do not necessarily mediate the negative feedback effects of steroids. Some other factor(s), as yet unidentified in the rat, may control the opioid modulation of gonadotrophin secretion or exert an independent inhibitory effect on gonadotrophin release.     

Amplification of pulsatile LH secretion by exogenous melatonin in women

The effect of melatonin on pulsatile LH secretion was investigated in early follicular phase women (days 2-5). During two consecutive days, at 0800 hrs., subjects received placebo or oral melatonin in a random double-blind fashion. Two doses of melatonin were used; 100 mg single dose (N = 6) or 2.5 mg in three divided doses (N = 5), (1 mg at 0800 hrs., 0.75 mg at 1000 and 1200 hrs.). Blood samples were collected every 10 minutes, between 0900-1700 hrs. Compared with placebo, melatonin administration augmented LH pulse amplitude (p less than 0.01) without changing LH pulse frequency. The integrated LH secretion was significantly increased (p less than 0.01) after melatonin, independent of doses administered. Serum FSH and ovarian steroids were not altered. It is concluded that exogenous melatonin enhances LH pulse amplitude in women, without modifying FSH and ovarian steroid levels.     

Endogenous opioid regulation of pulsatile luteinizing hormone secretion during sexual maturation in the female sheep

The developing female sheep, which attains puberty after 25 weeks of age, was used as an experimental model to investigate the role of endogenous opioid peptides in the control of pulsatile LH secretion during sexual maturation. Treatment of ovary-intact prepubertal sheep at 12 weeks of age with the opiate antagonist naloxone resulted in a dose-dependent increase in LH secretion. Subsequent studies used ovariectomized (OVX) lambs implanted with capsules containing 17 beta-estradiol to provide a constant, ovarian steroid feedback signal throughout development. Naloxone treatment (hourly iv injections of 1 mg/kg BW for 4 h) produced an increase in the frequency of episodic LH secretion at all prepubertal ages, when lambs were highly sensitive to the estradiol negative feedback. However, increases in LH pulse frequency were also induced by naloxone treatment at a postpubertal age in estradiol-treated OVX sheep, indicating that opioid inhibition is still present at a time when sensitivity to the feedback effects of ovarian steroids is markedly reduced and endogenous LH secretion is increased. These observations in ovary-intact and estradiol-treated OVX lambs suggest that opioid mechanisms inhibit pulsatile tonic LH secretion during both the prepubertal and postpubertal periods. Endogenous opioid inhibition of LH secretion is not dependent on the presence of ovarian steroids, as evidenced by the response to naloxone 3 weeks after removal of an estradiol implant from OVX lambs, when LH pulse frequency was already high. Naloxone treatment increased LH pulse frequency further, at both a prepubertal age (18 weeks) and a postpubertal age (38 weeks). Naloxone also increased LH pulse frequency in OVX lambs in which LH secretion was inhibited chronically by progesterone rather than by estradiol. The response to naloxone was similar in postpubertal P-treated OVX lambs and age-matched prepubertal P-treated OVX controls in which puberty had been delayed by means of an inhibitory seasonal photoperiod. In addition, after removal of steroid implants to allow LH secretion to increase, the degree of inhibition of LH secretion by the opiate agonist morphine was similar between age-matched postpubertal sheep and those with photoperiodically delayed puberty. We conclude that endogenous opioid mechanisms are an important inhibitory mechanism controlling pulsatile LH secretion in the developing sheep. However, changes in opioid inhibition are unlikely to underlie the decrease in sensitivity to steroid negative feedback and increase in pulsatile LH secretion that occur at puberty.     

Stimulatory or inhibitory effects of angiotensin II upon LH secretion in ovariectomized rats: a function of gonadal steroids

The effects of intraventricular infusions of artificial cerebrospinal fluid (aCSF) or angiotensin II (AII) on LH secretion were investigated in rats that had been ovariectomized for 8 days. In untreated ovariectomized rats, the mean whole blood concentration of LH as well as the amplitude, frequency, and nadir of the LH pulses were not affected by infusion of aCSF or 15 ng AII/h, but were suppressed in a dose-dependent fashion by infusion of AII at doses of 150 or 600 ng/h. The AII receptor antagonist, saralasin, blocked the inhibitory effect of AII, demonstrating the specificity of the response to AII. In ovariectomized rats pretreated with estradiol, infusion of AII did not modify mean blood LH levels. However, in ovariectomized rats pretreated with both estradiol and progesterone, infusions of AII at 150 or 600 ng/h produced dose-dependent increases in mean LH concentrations. The results demonstrate both inhibitory and stimulatory effects of AII upon LH secretion, the direction of the effect being determined by gonadal steroids.     

Increases in testosterone secretion in adult rams with immunoneutralization of endogenous estradiol occur in the absence of increases in pulsatile LH release or testicular LH receptors

The testes of the ram become more responsive to LH stimulation following immunoneutralization of endogenous estradiol. The possibility that testosterone secretion is facilitated by increased LH-binding activity in the testes was investigated in the present study conducted with adult Dorset X Leicester X Suffolk rams during the time of testicular recrudescence. Patterns of episodic LH release and testosterone secretion (days--5, 10 and 24) and LH-binding activity in testicular biopsy samples (days--1, 14 and 28) were assessed on the days indicated relative to the onset of passive immunization and the establishment of relatively low titres (approximately 1:200) of estradiol antiserum. During the experimental period, mean serum testosterone concentration increased by approximately 150% for the immunized rams as basal concentration and pulse amplitude increased, while all characteristics of testosterone secretion remained unchanged for the nonimmunized rams. Characteristics of LH release and the concentration of LH-binding sites in the testes, however, were always similar for both groups of rams. Further, group differences in FSH and PRL secretion and in the concentration of testicular FSH-binding sites did not occur. These results provide evidence for an estradiol direct (gonadotropin independent) negative-feedback component in the regulation of Leydig cell function in the ram.     

Feedback regulation of pulsatile LH secretion in the ewe: stimulation of frequency by estradiol

This study tested the hypothesis that estradiol can enhance LH pulse frequency in the ewe by an action which does not depend on other ovarian hormones. Long-term ovariectomized ewes were treated with a small subcutaneous estradiol implant at a time equivalent to the early breeding season (October), and frequent blood samples (6-min intervals) were obtained during sequential 3-hour periods over the next 84 h. All ewes responded with an increase in frequency of LH pulses, a response evident by 60 h and maintained at 84 h after initiation of the estradiol stimulus. Mean (+/- SE) pretreatment frequency was one pulse every 41 +/- 2 min; that at the height of the response was one pulse every 34 +/- 2 min (p less than 0.01). This increased rate was equivalent to the annual mid-winter maximum observed in ovariectomized ewes not treated with estradiol. These findings are consistent with the hypothesis that estradiol can enhance LH pulse frequency by an action which does not depend on other ovarian steroids. It is suggested that this action contributes to the heightened pace of LH pulses during the follicular phase of the estrous cycle.     

Short-term effects of ovariectomy: the opioid control of LH secretion in fertile climacteric and postmenopausal women

The aim of this study was to evaluate the activity of opiate receptors involved in the regulation of LH secretion in relationship to ovariectomy. Menstruating fertile (n = 5) and climacteric (n = 7) patients and postmenopausal (n = 5) women who underwent therapeutical bilateral ovariectomy were studied in the first week postsurgery and LH plasma levels were evaluated after naloxone (4 mg in bolus plus 4 mg infusion/90 min), LHRH (10 micrograms + 10 micrograms iv) and saline administration. Two groups of fertile (n = 6) and postmenopausal (n = 6) subjects were studied as controls. Since the LH responsiveness to naloxone was impaired in climacteric patients after ovariectomy, the test was repeated in 5 of them after 1 and 6 months of estrogen-gestagen treatment (conjugated estradiol + noretisterone acetate), showing a significant increase in all patients in both cases. In four subjects treated with only gestagen, naloxone was still unable to significantly modify LH plasma levels. These results indicate that ovariectomy affects the activity of opiate receptors, resulting in the first week postsurgery LH rise inversely related to basal LH levels. Furthermore, these results indicate that one or six cycles of estrogen-gestagen treatment in ovariectomized patients similarly induces a restoration of the opiate receptors neuroendocrine activity.     

Modulation of gonadotropin secretion by corticosterone: interaction with gonadal steroids and mechanism of action

The effects of corticosterone (B) on pituitary responsiveness to LHRH and on gonadal steroid modulation of gonadotropin secretion were investigated using primary cultures of rat pituitary cells. Cultures were treated for 2 days with steroids and then challenged with LHRH for 4 h. B inhibited LH secretion, increasing the EC50 for LHRH from 1.40 to 4.96 nM. The reduction in LH release was accompanied by an increase in cell LH, so that the total amount of LH present in the cultures was unchanged. The EC50 for the effect of B on LH secretion was 0.57 microM. B increased the total amount of FSH present in the cultures. At high concentrations of B (10-100 microM), this effect was associated with an increase in FSH secretion. Testosterone inhibited LH secretion in both the absence and the presence of B. B had no effect in the presence of maximal concentrations of testosterone but augmented the inhibitory effect of lower concentrations. Estradiol (E) stimulated LH secretion in both the absence and the presence of B. However, the stimulatory effect of E was reduced by B, so that cultures treated with both B and E secreted no more LH than untreated cultures. B inhibited the LH secretory responses to Ca2+ influx and protein kinase C activation but did not affect the response to arachidonic acid, suggesting that the mechanism of B action may involve an inhibition of arachidonic acid release. Together these results indicate that the inhibitory effects of stress on reproduction are mediated at least partially by the inhibitory effects of B on LH secretion.     

Intracellular receptors mediate gonadal steroid modulation of LHRH-induced LH release

Primary cultures of enzymatically dispersed rat pituitary cells were used to study the role of intracellular receptors in gonadal steroid modulation of LHRH-induced LH release. Nuclear receptors for both testosterone (T) and 17β-estradiol (E) were observed, with K_D values of 6.3 and 0.1 nM respectively. Occupation of these receptors was correlated with modulation of LH secretion. The relationship between these two parameters was nonlinear, so that steroid effects on LH secretion were maximal when fewer than 50% of the receptors were occupied. The androgen antagonist cyproterone blocked both T binding to nuclear receptors and T inhibition of LH secretion. Similarly, the estrogen antagonist CI-628 blocked both E binding and E stimulation of LH secretion. In cultures derived from pseudohermaphrodite rats, T did not bind to nuclear receptors, nor did it inhibit LH secretion. These results, showing a relationship between occupation of nuclear receptors and modulation of LH secretion, suggest that steroid effects on LH secretion are mediated by these receptors.     

Absence of regular pulsatile LH secretion during pre- and post-implantation periods in sheep

Two experiments were conducted to determine the patterns of LH secretion and to evaluate the LH responses to pulsatile administration of GnRH during early pregnancy in ewes. In experiment 1, pregnant ewes (n=16) were used to determine the concentration of LH in plasma of jugular blood samples collected every 15 min for 6h before (day 10 post-mating) and after (days 20 and 30 post-mating) implantation. In experiment 2, the pituitary LH responses to exogenous pulsatile administration of GnRH were examined on day 10 post-mating in 4 pregnant ewes. A small dose of GnRH (200 ng/ml saline) was injected (i.v.) every 3h and jugular blood samples were collected every 15 min for 12h beginning at the onset of GnRH administration and continuing through the 4th GnRH pulse. During the frequent-sample bleeding at any of the stages of pregnancy examined, LH concentrations oscillated in a pulsatile manner. However, pulsatile LH release occurred irregularly and infrequently. Overall mean LH concentrations, frequency and amplitude of LH pulses were not significantly different between any of the stages of pregnancy examined. Pulsatile administration of GnRH on day 10 post-mating induced regular pulses of LH. In conclusion, these data demonstrate that: (i) pulsatile LH secretion occurs irregularly during early pregnancy, and (ii) the absence of regular pulsatile LH release during early pregnancy is not attributed to a lack of pituitary responsiveness to GnRH.     

Gonadal steroid modulation of LHRH-stimulated LH secretion by pituitary cell cultures

Enzymatically dispersed rat pituitary cells were grown in primary culture, and LHRH-stimulated LH secretion was measured. Testosterone (T) decreased and 17 beta-estradiol (E) increased pituitary responsiveness to LHRH. The effect of E on LH secretion was partly due to an increase in LH content. There was a latent period of 12 h for E and 18 h for T between the onset of steroid treatment and the manifestation of steroid action. Neither steroid was required to be continuously present in order to exert its effects. After steroid withdrawal, the effect of T persisted for 72 h and that of E for more than 96 h. The actions of both steroids were blocked by protein-synthesis inhibitors. These results are consistent with the hypothesis that steroid effects rely on a mechanism involving alterations in protein synthesis; the affected proteins may be involved in the process of LHRH action.     

Fasting impairs LH secretion in female rats by activating an inhibitory opioid pathway

Two experiments were undertaken to investigate the way that fasting impairs LH secretion and to assess whether endogenous opioid mechanisms might be responsible for the impairment. In the first experiment, pulsatile LH secretion was measured in a total of 51 chronically ovariectomized female rats. Initially 29 rats were subjected to food withdrawal for 24, 48, 72 or 120 h before the experiment. When compared with data collected from eight unfasted control rats, the 120-h fast was found to reduce significantly the mean peak and trough values of the LH pulses measured. However, in a subsequent study, the inhibition of pulsatile LH secretion by a 120-h fast was prevented in a group of eight rats given the opioid antagonist naloxone hydrochloride before the start of the blood-sampling period. Naloxone was without effect on pulsatile LH secretion in eight unfasted control rats. In the second experiment, plasma LH concentrations were measured before and after unilateral electrical stimulation of the ventral noradrenergic tract (VNAT) in ovariectomized female rats pretreated with oestradiol benzoate. In 17 rats VNAT stimulation caused a significant rise in plasma LH, but after a 72-h fast this rise was significantly less than in unfasted control rats. However, pretreatment of fasted rats with naloxone (n = 9) significantly enhanced the VNAT-stimulated release of LH to the control values. Naloxone did not potentiate VNAT-stimulated LH release in unfasted animals (n = 6) or LH release in control unstimulated rats (n = 12). The experiments indicate that both pulsatile LH secretion, and LH release caused by VNAT stimulation, are impaired by an acute fast.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progesterone modulation of pulsatile luteinizing hormone secretion in normal women

Recent studies show that the frequency and amplitude of pulsatile LH secretion change during the normal human menstrual cycle; however, the neuroendocrine mechanisms underlying these changes are poorly understood. To assess the role of progesterone (P) in regulating LH secretion patterns, we treated normal women (n = 5) with im P in oil during the follicular phase of their cycle and compared LH pulse frequency, amplitude, and mean plasma level during treatment to those in normal cycling women. Normal women were studied five times in five menstrual cycles. Each study lasted 24 h, with a sampling interval of 20 min. The cycle phases studied were early follicular (twice), late follicular (LF), midluteal, and LF with P therapy to simulate luteal phase plasma P levels. LH pulse frequency was slower (P less than or equal to 0.001) in the midluteal phase than in either the early follicular phase or LF, and furthermore, P, administered in the normal follicular phase, slowed LH pulse frequency, augmented pulse amplitude, and reduced mean plasma LH levels compared to those in untreated women studied at the same cycle phase (P less than or equal to 0.02). We infer that P secretion by the ovary mediates the change in the LH secretory pattern during the luteal phase of the normal menstrual cycle, and that at least part of this effect is mediated by the central nervous system.