Luteinizing Hormone Interpulse Interval Research Articles

A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women.

We examined the effects of 1 month of a eucaloric, high-fat (48% of calories) diet (HFD) on gonadotropin secretion in normal-weight women to interrogate the role of free fatty acids and insulin in mediating the relative hypogonadotropic hypogonadism of obesity. Eighteen eumenorrheic women (body mass index [BMI] 18-25 kg/m2) were studied in the early follicular phase of the menstrual cycle before and after exposure to an HFD with frequent blood sampling for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), followed by an assessment of pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Mass spectrometry-based plasma metabolomic analysis was also performed. Paired testing and time-series analysis were performed as appropriate. Mean endogenous LH (unstimulated) was significantly decreased after the HFD (4.3 ± 1.0 vs. 3.8 ± 1.0, P < 0.01); mean unstimulated FSH was not changed. Both LH (10.1 ± 1.0 vs. 7.2 ± 1.0, P < 0.01) and FSH (9.5 ± 1.0 vs. 8.8 ± 1.0, P < 0.01) responses to 75 ng/kg of GnRH were reduced after the HFD. Mean LH pulse amplitude and LH interpulse interval were unaffected by the dietary exposure. Eucaloric HFD exposure did not cause weight change. Plasma metabolomics confirmed adherence with elevation of fasting free fatty acids (especially long-chain mono-, poly-, and highly unsaturated fatty acids) by the last day of the HFD. One-month exposure to an HFD successfully induced key reproductive and metabolic features of reprometabolic syndrome in normal-weight women. These data suggest that dietary factors may underlie the gonadotrope compromise seen in obesity-related subfertility and therapeutic dietary interventions, independent of weight loss, may be possible.

Undernutrition reduces kisspeptin and neurokinin B expression in castrated male sheep.

SummaryUndernutrition impairs reproductive success through suppression of gonadotropin-releasing hormone (GnRH), and subsequently luteinizing hormone (LH), secretion. Given that kisspeptin and neurokinin B (NKB) neurons in the arcuate nucleus (ARC) of the hypothalamus are thought to play key stimulatory roles in the generation of GnRH/LH pulses, we hypothesized that feed restriction would reduce the ARC mRNA abundance and protein expression of kisspeptin and NKB in young, male sheep. Fourteen wethers (castrated male sheep five months of age) were either fed to maintain (FM; n = 6) pre-study body weight or feed-restricted (FR; n = 8) to lose 20% of pre-study body weight over 13 weeks. Throughout the study, weekly blood samples were collected and assessed for LH concentration using RIA. At Week 13 of the experiment, animals were killed, heads were perfused with 4% paraformaldehyde, and brain tissue containing the hypothalamus was collected, sectioned, and processed for detection of mRNA (RNAscope) and protein (immunohistochemistry) for kisspeptin and NKB. Mean LH was significantly lower and LH inter-pulse interval was significantly higher in FR wethers compared to FM wethers at the end of the experiment (Week 13). RNAscope analysis revealed significantly fewer cells expressing mRNA for kisspeptin and NKB in FR wethers compared to FM controls, and immunohistochemical analysis revealed significantly fewer immunopositive kisspeptin and NKB cells in FR wethers compared to FM wethers. Taken together, this data supports the idea that long-term feed restriction regulates GnRH/LH secretion through central suppression of kisspeptin and NKB in male sheep.Lay summaryWhile undernutrition is known to impair reproduction at the level of the brain, the components responsible for this in the brain remain to be fully understood. Using male sheep we examined the effect of undernutrition on two stimulatory molecules in the brain critical for reproduction: kisspeptin and neurokinin B. Feed restriction for several weeks resulted in decreased luteinizing hormone in the blood indicating reproductive function was suppressed. In addition, undernutrition also reduced both kisspeptin and neurokinin B levels within a region of the brain involved in reproduction, the hypothalamus. Given that they have stimulatory roles in reproduction, we believe that undernutrition acts in the brain to reduce kisspeptin and neurokinin B levels leading to the reduction in luteinizing hormone secretion. In summary, long-term undernutrition inhibits reproductive function in sheep through suppression of kisspeptin and neurokinin B within the brain.

LH secretion and testosterone concentrations are blunted after resistance exercise in men.

This study examined the hypothesis that exercise-induced changes in circulating testosterone would be centrally mediated via hypothalamic-pituitary release of luteinizing hormone (LH). We tested this hypothesis by examining overnight LH, total and free testosterone (TT and FT), and cortisol (C) concentrations in 10 young healthy men (21 +/- 1 yr) during two experimental sessions: a control and an acute heavy-resistance exercise bout (50 total sets consisting of squats, bench press, leg press, and latissimus dorsi pull-down). Exercise was performed from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the next morning. Blood was sampled every 10 min for LH and every hour for TT, FT, and C. Hormonal concentrations were determined via RIA, and the secretion characteristics of LH were analyzed with deconvolution analysis. When overnight postexercise concentrations were compared with control concentrations, no statistically significant (P < or = 0.05) differences were observed for LH half-life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass. Significant differences were observed for LH production rate (13.6 +/- 4 and 17.9 +/- 5 IU. l distribution volume(-1) x day(-1) for exercise and control, respectively, a 24% reduction). For the ANOVA marginal main effect means due to condition, C was significantly elevated (5.9 +/- 0.7 vs. 4.0 +/- 0.4 microg/dl), while TT (464 +/- 23 vs. 529 +/- 32 ng/dl) and FT (15.6 +/- 0.7 vs. 18.3 +/- 0.9 pg/ml) were significantly decreased for the exercise condition. These data demonstrate that the decline in overnight testosterone concentrations after acute heavy-resistance exercise is accompanied by a blunted LH production rate and elevated C concentrations.

Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions.

We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the alpha1 and alpha2 but not beta receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an alpha1- or alpha2-adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by alpha1 and alpha2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate-serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems.

Temporal effects of estradiol (E) on luteinizing hormone-releasing hormone (LHRH) and LH release in castrated male sheep

We tested the hypothesis that rapidly expressed inhibitory effects of estradiol (E) on luteinizing hormone (LH) release in the male are attributable, in part, to suppression of luteinizing hormone-releasing hormone (LHRH) release. Hypophyseal-portal cannulated, castrated male sheep were infused with E (15 ng/kg/hr) or vehicle. Portal and jugular blood samples were collected at 10-min intervals for 4 hr before, and for either 12 hr (E, n = 4; vehicle, n = 4) or 24 hr (E, n = 8; vehicle, n = 3) after the start of infusion. In animals sampled for 16 hr, temporal changes in both LHRH and LH were assessed. In animals sampled for 28 hr, only LH data were analyzed. Before either the 12-hr or 24-hr infusion, LHRH and/or LH mean concentrations, pulse amplitude and interpulse interval (IPI) did not differ between E- and vehicle-infused animals. In animals sampled for 16 hr, no effects of time or steroid × time interactions were detected for mean LHRH and LHRH pulse amplitude; however, both were greater (P < 0.01) in vehicle-infused than in E-infused males. LHRH IPI was unaffected by infusion. In contrast, both mean LH and LH pulse amplitude declined (P < 0.01) within 4–8 hr after the start of E infusion, whereas mean LH IPI was unaffected. In animals sampled for 28 hr, an effect of time (P < 0.01) and a steroid × time interaction (P < 0.01) was detected for mean LH, and there was an effect of time (P < 0.01) on LH pulse amplitude. Mean LH IPI was not affected. Our results show that in male sheep E rapidly reduces LH release in the absence of a detectable change in LHRH release.

Luteinizing and follicle-stimulating hormone secretion during median eminence perfusion or intravenous infusion with gonadotrophin-releasing hormone antisera in ovariectomized ewes

Effects of passive immunization against gonadotrophin-releasing hormone (GnRH) on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion were examined in six ovariectomized (OVX) ewes during the breeding season (8L:16D). The same amount of rabbit anti-GnRH serum was administered by intravenous infusion or median eminence (ME) perfusion over 30 h. Administration of anti-GnRH serum by both routes failed to affect FSH ( P>0.05) but equally reduced basal and mean circulating LH concentrations and LH pulse amplitude ( P<0.05). Luteinizing hormone pulse amplitude was also reduced by ME perfusion with vehicle ( P<0.05). Luteinizing hormone interpulse interval was not affected by intravenous infusion with anti-GnRH serum but was increased by ME perfusion with anti-GnRH serum ( P<0.05). The results suggested that targeting the ME of the ovariectomized ewe with perfusion of GnRH antiserum for 30 h blocked pulsatile LH secretion, leaving only basal secretion, and had no effect on FSH secretion.

Seasonal fluctuation in diurnal rhythms of luteinizing hormone secretion in ewes during the mid-luteal phase of the oestrous cycle.

Diurnal and seasonal fluctuations were detected in luteinizing hormone (LH) interpulse interval, but not amplitude, in ewes examined during the mid-luteal phase of an oestrous cycle at five stages of the breeding season. Daytime and night-time LH interpulse intervals were greater in the early and late than in the mid-breeding season (P < 0.05). During the early and late breeding season, LH interpulse interval was less during daylight than during darkness (P < 0.05). Toward the mid-breeding season, interpulse interval decreased during daytime earlier in the season than the night-time decrease. It was concluded that the diurnal fluctuations observed are a component of a circannual rhythm in LH secretion resulting from gradual seasonal transitions in photoperiodic drive to, or an endogenous rhythm in, the hypothalamic-pituitary axis in ewes.

Evidence that Dopaminergic Neurons are not Involved in the Negative Feedback Effect of Testosterone on Luteinizing Hormone in Rams in the Non‐Breeding Season

In this study we tested the hypothesis that the negative feedback effects by testosterone on the secretion of luteinizing hormone (LH) in rams involves dopaminergic afferents to gonadotrophin-releasing hormone neurons operating via D(2) receptors in the non-breeding season. In the first experiment, three groups (n = 5) of rams were treated with an intravenous injection of vehicle or 10 or 20 mg of the dopaminergic D(2) antagonist pimozide and jugular venous samples were collected every 10 min for 3 h before and 3 h following treatment. The plasma was assayed for LH. Three groups of ewes (n = 4 to 5) were similarly treated. There were no significant effects of treatment of the rams with pimozide on the plasma concentrations of LH or LH pulse frequency or pulse amplitude and the response of individual rams in each group was inconsistent. In contrast, treatment of the ewes with 20 mg pimozide significantly (P<0.001) increased the mean (± SEM) plasma LH concentrations (pretreatment 0.37 ± 0.04; post-treatment 2.42±0.25 ng/ml) and decreased (P<0.001) the LH inter-pulse interval (pretreatment 180.0; post-treatment 88.0±11.1 min); the 10 mg dose of pimozide did not affect these parameters. In the second experiment, two groups of rams (n = 5) and ewes (n = 7) were treated with an intravenous injection of vehicle or 0.33 mg pimozide/kg liveweight and jugular venous samples were collected every 10 min for 2 h before and 6 h following treatment. As in the first experiment, the mean (± SEM) concentrations of plasma LH were not affected by treatment with pimozide in the rams (pretreatment 0.18 ± 0.25; post-treatment 0.43 ± 0.14 ng/ml) but were significantly (P<0.05) increased in the ewes (pretreatment 1.12±0.22; post-treatment 1.93 ± 0.23 ng/ml). In the third experiment, four adult rams were castrated and 3 weeks later each animal had two cannulae inserted to allow injection into the lateral cerebral ventricles. Vehicle or 100 μg pimozide was injected intracerebroventricularly and blood samples were collected as in the other experiments. A Latin Square design was used so that each animal received each treatment (n = 4). This procedure was repeated after the animals had been injected (intramuscularly) with 16 mg testosterone propionate twice daily for at least 7 days. Treatment with testosterone propionate significantly decreased (P < 0.001) the plasma concentrations of LH (pre-treatment 7.71±0.27; post-treatment 0.75 ± 0.27 ng/ml; mean ± SEM) and follicle-stimulating hormone (pre-treatment 79.61±8.47; post-treatment 42.53 ± 6.08 ng/ml; mean ± SEM) and increased the mean (± SEM) LH inter-pulse interval (53.14 ± 3.58 min pre-treatment and 292.5 ± 32.94 min post-treatment) but had no effect on the amplitude of LH pulses (pre-treatment 3.61 ± 0.36; post-treatment 1.86±1.76 ng; mean ± SEM). Pimozide had no effect on the plasma concentrations of gonadotrophins. These results suggest that, in the ram, dopaminergic neurons do not influence the gonadotrophin-releasing hormone neurons via D(2) receptors in the non-breeding season and are not involved in the negative feedback effect of testosterone on the secretion of gonadotrophins. Conversely, our data suggest that such a mechanism is integral to the negative feedback effects of oestradiol on LH in anoestrous ewes. Finally, it also appears that the steroid-independent suppression of the secretion of gonadotrophins during the non-breeding season in rams is not mediated via D(2) receptors.

Effects on Plasma Luteinizing Hormone Levels of Microinjection of Noradrenaline and Adrenaline into the Septo‐Preoptic Area of the Brain of the Ovariectomized Ewe: Changes with Season and Chronic Oestrogen Treatment

We have investigated the effects on luteinizing hormone (LH) secretion of noradrenaline (NA) and adrenaline (A) microinjected (1 μl) into the septo-preoptic area of ovariectomized (OVX) ewes with or without oestrogen (E) treatment and across the breeding and non-breeding seasons. Guide tubes (19 gauge) were placed into the septo-preoptic area of OVX ewes using lateral ventriculograms for localization of the target area. The sheep were tamed so that injections could be made into conscious animals during blood sampling procedures. Jugular venous blood was collected at 10-min intervals for 3 h, an injection of NA or A (10 μg) or saline was given and samples collected for a further 3 h. The plasma samples were assayed for LH. On completion of the experiments the brains were sectioned to locate the site of injection. In the non-breeding season of the first year, 9 ewes were used of which 3 had correct guide tube placement; in these 3 ewes NA and A had no effect in OVX ewes. In OVX ewes treated with 0.5 cm Silastic ®implants of E for 1 week, plasma LH levels were reduced from 9.1 ± 1.96 nglrnl before E treatment to 2.8±0.95 ng/ml after E treatment. In these E-treated ewes NA and A caused a robust increase in plasma LH levels. In the breeding season, 9 ewes were used of which 7 had correct guide tube placement; in these 7 ewes NA and A had no effect in OVX ewes. When OVX ewes were treated with 0.5cm E implants, NA or A injection decreased LH interpulse interval. In OVX ewes which received 1.0 cm E, NA caused a pronounced but transient suppression of plasma LH secretion due to an increase in interpulse interval. When 3.0 cm E implants were given to OVX ewes there was a strong suppression of plasma LH secretion with pulsatility abolished; NA injection had no effect in these sheep. In the second year, in the non breeding-season, 17 ewes were used of which 14 had correct guide tube placement although a number of injections were above the target region. NA injection had no effect on plasma LH levels in OVX ewes but had a variable effect on OVX ewes treated with 0.5 cm E implants, depending upon the degree of suppression of plasma LH secretion by E. When plasma LH was fully suppressed by E, injection of 1Opg NA provoked a profound and sustained increase in plasma LH levels. When plasma LH secretion was pulsatile after E treatment, NA injection decreased LH interpulse interval. Similar responses were obtained with 0.5cm E-treated sheep when injected with 1.Opg NA. When OVX ewes were given 3.0cm E implants a small and non-significant (P = 0.09) rise in plasma LH levels occurred, following 10 pg NA injection. These results provide further evidence of involvement of NA/A systems in the regulation of gonadotrophin-releasing hormone (GnRH) secretion at the level of the GnRH cell bodies in the septo-preoptic area, with clear influences of season and E status on this regulation. In the OVX sheep the GnRH pulse generation system is probably subserved by endogenous permissive NA/A input rendering exogenous input ineffective. In the breeding season NAlA can inhibit GnRH/LH secretion in the presence of physiological doses of E whereas in the non-breeding season, E profoundly suppresses GnRH/LH secretion, possibly by the removal of permissive NA inputs, which can be overcome by the injection of NAlA into the septo-preoptic area.

Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult-onset congenital adrenal hyperplasia?

To assess gonadotropin alterations in adult-onset congenital adrenal hyperplasia (CAH) and to compare these findings with those of patients with polycystic ovary syndrome (PCOS) in an effort to better understand the pathophysiology of these abnormalities. Prospective study of 9 newly diagnosed patients with CAH, 10 with PCOS, and 10 ovulatory controls. Baseline measurements of serum androgens, progestins, estradiol (E2), estrone (E1), unbound E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Serum LH and FSH were measured after intravenous gonadotropin-releasing hormone (GnRH) and in 15-minute blood samples for 6 hours to determine LH pulsatility. Serum androgens were elevated but comparable in the two patient groups. Serum LH was also elevated (P less than 0.05) but was higher in PCOS than CAH. Serum LH:FSH ratios were similar as were the responses to GnRH. Serum E1 was elevated only in PCOS, but unbound E2 was elevated to the same degree in both PCOS and CAH (P less than 0.05). Patients with PCOS had a decreased LH interpulse interval compared with controls and CAH (P less than 0.05), but LH pulse amplitude was increased in both PCOS and CAH (P less than 0.05). Serum E2 and unbound E2 correlated significantly with LH (P less than 0.05), LH responses to GnRH as well as to LH pulse amplitude in CAH (P less than 0.05). The LH interpulse interval did not correlate with estrogen in any group. None of the LH parameters correlated with serum progestin levels in CAH. The gonadotropin abnormalities of CAH appear to be intermediate between those of controls and PCOS. Although elevated estrogen may explain these abnormalities in CAH, additional factors may be operative in PCOS.

Short-term modulation of gonadotropin secretion by progesterone during the luteal phase

Progesterone (P) levels were acutely augmented by intravenous (IV) infusion in seven women in the midluteal phase to ascertain if short-term changes in P levels have an effect on gonadotropin secretion. During four 6-hour intervals of alternating control and IV P infusion, each subject underwent blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and P every 20 minutes for 24 hours. As a result of the P infusions, mean (+/- SE) P levels rose 72% from a control level of 26.24 +/- 2.13 to 45.22 +/- 3.47 nmol/L, whereas mean LH levels were reduced by 20% from a control level of 4.82 +/- 0.67 to 3.85 +/- 0.66 IU/L. During P infusions, mean LH pulse amplitude was reduced by 33% from 3.33 +/- 0.37 to 2.23 +/- 0.28 IU/L. The mean LH interpulse interval increased by 93% (2.56 +/- 0.14 to 4.92 +/- 0.15/h) when the interval between pulses was interdicted by the onset of P infusion. The infusion of P reduced mean FSH levels by 10% from 3.34 +/- 0.41 to 3.01 +/- 0.35 IU/L. These findings suggest that acute elevations in P levels within the physiological range have a short-term inhibitory effect on gonadotropin secretion during the midluteal phase.

Effects of progesterone on pulsatile luteinizing hormone (LH) secretion and LH subunit messenger ribonucleic acid during lactation in the rat.

In ovarian-intact lactating rats, removal of the suckling stimulus leads to restoration of pituitary LH beta mRNA levels and pulsatile LH secretion after 72 h, which correlates with a sharp decrease in plasma progesterone concentrations to basal levels. In contrast, in ovariectomized lactating rats, the increase in pituitary LH function is observed by 24 h after pup removal. To determine if progesterone secretion from the ovary participates in the delayed recovery of LH secretion, we treated lactating rats with the progesterone antagonist RU 486 and determined the effects on the time course of recovery of pulsatile LH secretion and LH subunit mRNA after pup removal and on pituitary responsiveness to GnRH. In ovarian-intact lactating rats treated with RU 486, pulsatile LH secretion was observed in about 40% of the rats within 24 h after pup removal (LH interpulse interval, 43.7 +/- 8.3 min) and in about 90% of the rats within 48 h after pup removal (LH interpulse interval, 46.1 +/- 3.6 min). The mean plasma LH level in the RU 486-treated rats was 10.1 +/- 2.2 ng/ml 24 h after removal of pups (control, less than 5 ng/ml) and had increased to 35.1 +/- 6.4 ng/ml 48 h after pup removal (control, 9.1 +/- 2.5 ng/ml). However, RU 486 treatment had no significant effect on LH mRNA subunit levels. To determine whether progesterone acts at the pituitary to block GnRH stimulation of LH secretion, we tested the effects of RU 486 on LH secretion in response to 2- and 5-ng pulses of GnRH. Pituitary responsiveness was tested 24 h after pup removal. We found that both doses of GnRH were effective in stimulating pulsatile LH secretion, and treatment with RU 486 had no significant effect on this response. We conclude from these studies that progesterone secretion from the ovary contributes to the inhibition of LH secretion that occurs after pup removal, since antagonizing progesterone's action resulted in an earlier restoration of pulsatile LH secretion. The increase in LH secretion occurred in the absence of any significant changes in responsiveness of the pituitary to GnRH stimulation or in LH subunit mRNA levels. Therefore, the primary site of action of progesterone would appear to be at the hypothalamus to suppress pulsatile GnRH secretion.

Suppression of pulsatile LH secretion, pituitary GnRH receptor content and pituitary responsiveness to GnRH by hyperprolactinemia in the male rat.

To assess whether gonadotropin-releasing hormone (GnRH) release from the hypothalamus might be altered by hyperprolactinemia in the male rat, we measured in chronically hyperprolactinemic rats the pituitary GnRH receptor content and described the pattern of luteinizing hormone (LH) release during the postcastration rise in gonadotropin secretion 24 and 72 h after gonadectomy. In intact rats, the effect of hyperprolactinemia was determined by describing the pattern of LH secretion, pituitary GnRH receptor content and assessment of pituitary responsiveness to small doses of GnRH (1.0 ng). In addition, to determine the role endogenous opioids might play in inhibiting GnRH release in hyperprolactinemic rats, we examined the effect of both a continuous infusion and a bolus injection of the opioid antagonist naloxone on the pattern of LH release. Chronic hyperprolactinemia was achieved by implanting 4 pituitaries under the kidney capsules 3-4 weeks before study. Acute hyperprolactinemia was achieved by injecting rats with 1 mg ovine prolactin every 12 h for 3 days. Control animals were untreated or were chronically hyperprolactinemic rats in which the hyperprolactinemia was transiently reversed by treatment for 3 days with the dopamine agonist 2-alpha-bromoergocryptine. The mean LH concentration was greatly decreased at 24 postcastration in chronically hyperprolactinemic rats relative to controls. This decrease was associated with a decrease in LH pulse height and pulse amplitude and pituitary GnRH receptor content, but not with an increase in the LH interpulse interval. In contrast, the decrease in mean LH concentrations in hyperprolactinemic animals at 72 h postcastration was primarily associated with a significantly longer LH interpulse interval than that observed in control animals. Chronic hyperprolactinemia in intact rats decreased the pituitary GnRH receptor content, in addition to decreasing the mean LH concentrations during pulsatile GnRH administration. Chronic hyperprolactinemia also inhibited LH release relative to controls during the continuous 4-hour infusion of naloxone and in response to a bolus injection of naloxone. However, in acutely hyperprolactinemic intact male rats a bolus injection of naloxone increase LH secretion 20 min later to levels similar to those obtained in control rats. In summary, these results indicate that chronic hyperprolactinemia decreased LH secretion by primarily decreasing GnRH secretion as suggested by a decrease in pituitary GnRH receptor content and a decrease in LH pulse frequency and pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)