Mean Luteinizing Hormone Pulse Amplitude 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.

The impact of undernutrition on KNDy (kisspeptin/neurokinin B/dynorphin) neurons in female lambs.

Undernutrition limits reproduction through inhibition of gonadotropin‐releasing hormone (GnRH)/luteinizing hormone (LH) secretion. Because KNDy neurons coexpress neuropeptides that play stimulatory (kisspeptin and neurokinin B [NKB]) and inhibitory (dynorphin) roles in pulsatile GnRH/LH release, we hypothesized that undernutrition would inhibit kisspeptin and NKB expression at the same time as increasing dynorphin expression. Fifteen ovariectomized lambs were either fed to maintain pre‐study body weight (controls) or feed‐restricted to lose 20% of pre‐study body weight (FR) over 13 weeks. Blood samples were collected and plasma from weeks 0 and 13 were assessed for LH by radioimmunoassay. At week 13, animals were killed, and brain tissue was processed for assessment of KNDy peptide mRNA or protein expression. Mean LH and LH pulse amplitude were lower in FR lambs compared to controls. We observed lower mRNA abundance for kisspeptin within KNDy neurons of FR lambs compared to controls with no significant change in mRNA for NKB or dynorphin. We also observed that FR lambs had fewer numbers of arcuate nucleus kisspeptin and NKB perikarya compared to controls. These findings support the idea that KNDy neurons are important for regulating reproduction during undernutrition in female sheep.

Role of progesterone concentrations during early follicular development in beef cattle: I. Characteristics of LH secretion and oocyte quality

Objective was to investigate the effect of different progesterone (P4) concentrations during early follicular development on luteinizing hormone (LH) secretion and oocyte characteristics in beef cows. Primiparous cows (n = 24) were estrous pre-synchronized and follicular ablation was performed (d 0) 6 days following the time of ovulation. At the time of follicular ablation, cows were assigned to either: 1) high P4 treatment - HiP4; a new CIDR was inserted on d 0 to supplement P4 from the existing corpus luteum [CL], or 2) low P4 treatment - LoP4; a previously-used CIDR and two doses of PGF 8 to 12 h apart were given on d 0. Concentrations of P4 were greater (P < 0.01) in the cows of the HiP4 than LoP4 group on d 1.5, 2.5, and 3.5. Peripheral concentrations of E2 were greater (P < 0.05) in the cows of the LoP4 than HiP4 group on d 2.5 and 3.5. Frequency of LH pulses was greater (P < 0.05) in the LoP4 than HiP4 group on d 2.5, but mean LH concentration and pulse amplitude did not differ between treatments. Number of follicles aspirated per cow, total oocytes recovered, recovery rate, percentage of oocytes graded 1 to 3, oocyte diameter, percentage BCB+ oocytes, and relative abundance of oocyte mRNA for FST did not differ (P > 0.10) between treatments. In conclusion, lower P4 concentrations during early follicular development resulted in increased LH pulse frequency and E2 concentrations, but did not affect characteristics of oocyte developmental competence.

Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome.

Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology.

Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women

To better understand the site and mode of action of aromatase inhibitors. Prospective study. Academic research environment. Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls. 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes. Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests. Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls. These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action.

MOLECULAR SPECIES OF PROSTAGLANDINS MEDIATING STRESS-INDUCED SUPPRESSION OF GONADOTROPIN SECRETION IN THE BRAIN

It is well established that reproductive function is suppressed under stress conditions. We have previously shown that all the infectious (lipopolysaccharide), hypoglycemic (2-deoxyglucose) and restraint stress suppressed pulsatile release of luteinizing hormone (LH), which was associated with an increase in cyclooxygenase-2 expression in the brain. The suppression of LH pulses by these stressors was much more enhanced by andrenalectomy. On the other hand, both corticosterone and indomethacin similarly attenuated the suppressive effect of the stressors on LH pulses. These observations suggest that prostaglandins (PG) are involved in stress-induced suppression of LH pulses. In the present study, in order to determine which subtype of PGs is involved in suppressing LH pulses, we intracerebroventricularly administered 3 major PG subtypes, i.e. PGF2α, PGD2, and PGE2. We observed LH pulses in ovariectomized rats for 3 hours by sequential blood sampling of 5 min-intervals. PGs were injected 1 h after the start of blood sampling. First, we treated animals with each PG in 3 increasing doses (0.1, 1 and 10 μg). PGF2α did not have any influence on LH pulsatility at all the doses used. PGD2 induced a dose-dependent increase in the amplitude of LH pulses while it did not affect the frequency of LH pulses and mean LH concentrations. On the other hand, PGE2 dose-dependently induced a transient increase and subsequent decreased in both mean LH concentrations and pulse amplitude, and strongly suppressed LH pulse frequency at the highest dose. Secondly, we co-injected PGF2α (5 μg) and PGE2 (5 μg), whose syntheses are known to simultaneously increase under infectious stress conditions. This resulted in a transient suppression of LH pulses in all the 3 parameters; frequency, amplitude, and mean concentrations. These results, together with our previous findings, suggest that PGE2, independently or together with PGF2α, in the brain plays a role in suppressing LH pulses as a common mediator of stressors, and that glucocorticoids maintain reproductive function by decreasing the synthesis of these PGs. (poster)

The GABA(B) antagonist CGP 52432 attenuates the stimulatory effect of the GABA(B) agonist SKF 97541 on luteinizing hormone secretion in the male sheep.

The objectives of this study were to determine if the gamma-aminobutyric acid (GABA)(B) agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would increase luteinizing hormone (LH) secretion when infused by microdialysis into the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the action of SKF97541 would be attenuated by co-infusion of the GABA(B) antagonist CGP52432. Initial experiments established that infusion of SKF alone, at concentrations as low as 5 microM, increased mean LH, LH pulse amplitude, and in some cases, pulse interval. In the last experiment, animals were treated with artificial cerebrospinal fluid (CSF) alone, SKF alone (30 microM), 3-[[(3, 4-dichlorophenol) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP) alone (500 microM), or SKF plus CGP. SKF increased both mean LH and LH pulse amplitude as compared with CSF. CGP alone had no significant effect on LH, but it attenuated the effect of SKF on mean LH. These observations indicate that the stimulatory effects of GABA(B) agonists on LH pulse patterns are mediated through GABA(B) receptors and provide further evidence that GABA(B) receptors located in the MBH can regulate pulsatile GnRH-LH release.

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.

Estradiol and gonadotropin-releasing hormone (GnRH) interact to increase GnRH receptor expression in ovariectomized ewes after hypothalamic-pituitary disconnection.

Gonadotropin-releasing hormone (GnRH) receptor expression is regulated by estradiol and GnRH itself. The objective of this experiment was to determine the extent to which low levels of estradiol, similar to those observed during the transition from the luteal to the follicular phase of the estrous cycle, and GnRH interact to regulate expression of GnRH receptors and GnRH receptor mRNA. Ewes were ovariectomized (OVX) at least 2 wk prior to initiation of the experiment, and the pituitary gland was surgically disconnected from the hypothalamus to remove ovarian and hypothalamic inputs to the pituitary. Within 24 h after hypothalamic-pituitary disconnection, ewes received pulses of GnRH (250 ng/pulse) every 2 h for 6 d. At the end of 6 d, ewes were randomly assigned to treatments in a 2 x 2 factorial arrangement as follows: half of the animals received a single estradiol implant and half received an empty implant (placebo). At the same time, animals also received one of the following treatments: (1) saline or (2) GnRH (100 ng/pulse/2 h). Additionally, one group of ewes was ovariectomized, but not subjected to hypothalamic-pituitary disconnection (OVX controls). Blood samples were collected 15 min prior to each pulse of GnRH or saline and at 15-min intervals for 1 h after each pulse until tissues were collected and concentrations of luteinizing hormone (LH) were determined. Anterior pituitaries were collected 24 h after implant insertion to quantitate steady-state amounts of GnRH receptor mRNA and numbers of GnRH receptors. Mean LH was greatest in ovariectomized control ewes compared to all other treatments (p < 0.05). Mean LH and LH pulse amplitude in the placebo and GnRH-treated group most closely mimicked LH secretion in ovariectomized control animals. Mean LH and LH pulse amplitude were similar between both GnRH-treated groups (p < 0.05). Mean LH and LH pulse amplitude were significantly lower in all animals treated with saline compared to OVX controls (p < 0.05). Treatment with an estradiol implant and pulsatile GnRH increased (p < 0.05) relative amounts of GnRH receptor mRNA and the number of GnRH receptors compared to all other treatments. There were no differences in GnRH receptor expression between the remaining treatment groups (p > 0.05). Therefore, in OVX ewes after hypothalamic-pituitary disconnection, low levels of estradiol and GnRH are required to increase GnRH receptor mRNA and GnRH receptor numbers. Since we only observed an increase in GnRH receptor expression in the presence of both estradiol and GnRH, we conclude that there is a synergistic interaction between these two hormones in the regulation of GnRH receptor expression.

Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys.

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.

Plasma Luteinizing Hormone Levels in Response to Gonadotropin-Releasing Hormone Agonist and Clonidine in Trypanosoma congolense-Infected Female Goats

Trypanosomiasis, a parasitic disease of humans and animals, occurs over a wide area of Africa and imposes a large socioeconomic burden on the people. In the present study, we investigated whether trypanosomiasis-induced reproductive disorders were due to pituitary or hypothalamic dysfunction by determining plasma luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) agonist or clonidine in Trypanosoma congolense -infected female goats. With GnRH agonist administration, the total amount of LH secreted over a 140-min sampling period on day 23 and day 60 postinfection was consistently higher (71 and 21%, respectively) in infected goats compared to controls. In contrast, clonidine administration to infected goats on day 28 and day 69 postinfection failed to significantly alter the LH pulse frequency or the mean LH pulse amplitude over a 80-min sampling period. The results, especially the lack of response to clonidine, indicate that trypanosomiasis impairs GnRH release from the hypothalamus.

Effect of undernutrition on pulsatile luteinizing hormone (LH) secretion in castrate and intact male rats using an ultrasensitive immunofluorometric LH assay.

The recent development of an ultrasensitive immunofluorometric rat LH assay makes possible evaluation of pulsatile LH secretion in intact male rats under physiological conditions of minimal volume blood sampling without requiring orchidectomy. Specifically, we applied this assay to determine the effect of macronutrient restriction on pulsatile LH secretion in the presence or absence of testes. In testes-intact rats, halving of food intake for 7 days while maintaining micronutrient supply caused a reduction of mean, maximal, and basal LH levels and LH pulse amplitude (all P < 0.05) compared with those in ad libitum fed controls. The loss of body weight was positively correlated with decreases in mean LH level, pulse amplitude, and area under the curve (all P < 0.009). In contrast, the same food restriction in castrated rats caused an increase in pulse length and area under the curve and a decrease in pulse frequency, but did not change mean, maximal, and basal LH levels or LH pulse amplitude compared to castrated ad libitum fed controls (all P < 0.02). The observed positive correlations between body weight and the LH secretion parameters in intact rats were absent or reversed in castrated rats. This study demonstrates qualitatively different effects of macronutrient restriction on pulsatile LH secretion in castrated and intact rats, indicating that it is not necessary valid to extrapolate consequences of undernutrition on LH secretion from castrate to intact male rats. We conclude that undernutrition-induced inhibition of LH secretion involves both an indirect suppression of LH secretion via amplification of endogenous testicular negative feedback as well as more direct suppression of GnRH release.

Effects of naloxone on circulating gonadotrophin concentrations in prepubertal heifers.

The pattern and opioidergic control of the secretion of gonadotrophins in prepubertal heifer calves were examined. Ten age-matched Hereford heifer calves were weighed and a blood sample was taken every 2 weeks from 2 to 25 weeks of age and then weekly until 60 weeks of age. At 60 weeks, a fertile bull was introduced and at 75 weeks of age pregnancy diagnosis was performed by transrectal ultrasonography. At 4, 12, 18, 24 and 32 weeks of age, the opioid antagonist naloxone was injected (i.v., n = 5; 1 mg kg-1 body weight) each hour for 12 h. Control heifers received sterile saline at the same ages. Blood samples were collected every 12 min for the 12 h treatment and serum samples were analysed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Samples taken once every 2 weeks from 2 to 60 weeks were analysed for LH, FSH and oestradiol, and weekly samples were taken for progesterone determination. There was no effect of naloxone on the age at puberty, which was 56.2 +/- 0.7 weeks at a body weight of 388.5 +/- 8.0 kg. The mean age at conception was 63.4 +/- 0.5 weeks. On the basis of samples taken every other week, serum concentrations of LH were high at 10 weeks and between 40 and 60 weeks of age. From the periods of intensive blood collection, the early rise in mean serum concentrations of LH appeared later at 12 and 18 weeks of age and was caused by a rise in LH pulse amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term changes in the quality and quantity of both trabecular and cortical bone in the young ovariectomized cynomolgus monkey: A comparison of histomorphometric and density fractionation techniques

It has been suggested that there is a difference in the interaction between sex steroids and gonadotropin secretion between transsexual and heterosexual women. In this study we tested whether there is a difference in the pulsatile release characteristics of luteinizing hormone (LH) and in ovarian steroid concentrations between 16 female-to-male (f-to-m) transsexuals and eight eugonadal heterosexual women during the early follicular phase of the menstrual cycle. Blood samples for LH determination were collected every 10 min for 7 hr in the transsexual group, and every 10 min for 6 hr in the heterosexual group. There were no significant differences between the transsexual and heterosexual group in mean serum LH concentration (6.9±2.4 U/l vs. 7.5±2.6 U/l), mean LH nadir interval (77±37 min vs. 70±16 min), and mean LH pulse amplitude (2.9±1.1 U/l vs. 3.0±1.1 U/l). Serum estrone, 17-β-estradiol, testosterone, progesterone and FSH concentrations also did not differ between the two groups. There also was not a higher prevalence of polycystic ovarian disease in our f-to-m transsexual group than in the general population.

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.

Opioidergic control of gonadotropin secretion in the female rabbit: divergent effects of morphine on secretion of follicle-stimulating hormone and luteinizing hormone

The nature of secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was followed in female rabbits on a daily basis from age 36 to 60 days by sequential 5-min blood sampling over 1- to 2-h periods each day. Both LH and FSH were found to be secreted in a pulsatile manner. The mean LH pulse amplitude over the 25 days was 0.95 +/- 0.32 ng/mL and for FSH it was 10.15 +/- 1.11 ng/mL. Mean plasma LH levels were significantly increased from 1.46 +/- 0.08 ng/mL in 36 to 42-day-old rabbits to 1.89 +/- 0.12 ng/mL in 43 to 50-day-old rabbits and remained elevated from 50 to 60 days. FSH levels during the same periods also rose significantly from 14.93 +/- 0.79 to 19.57 +/- 2.05 ng/mL. To examine the influence of endogenous opioid peptides on the release of LH and FSH in 36 to 60-day-old female rabbits, morphine sulfate at 0.2, 0.5, 2.0, and 5.0 mg/kg was administered subcutaneously after 30 min baseline sampling, and blood was taken for another 60-120 min. Morphine at all doses and at all ages inhibited the amplitude and frequency of LH pulses but had no effect on FSH secretion. To determine whether the effects of morphine on LH secretion could be reversed with naloxone, females aged 82-114 days were used. Naloxone administered 1 h after morphine reversed the inhibitory effects of morphine, whereas the simultaneous administration of naloxone with morphine had variable effects but seemed to delay the LH increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile luteinizing hormone release and ovarian steroid levels in female-to-male transsexuals compared to heterosexual women

It has been suggested that there is a difference in the interaction between sex steroids and gonadotropin secretion between transsexual and heterosexual women. In this study we tested whether there is a difference in the pulsatile release characteristics of luteinizing hormone (LH) and in ovarian steroid concentrations between 16 female-to-male (f-to-m) transsexuals and eight eugonadal heterosexual women during the early follicular phase of the menstrual cycle. Blood samples for LH determination were collected every 10 min for 7 hr in the transsexual group, and every 10 min for 6 hr in the heterosexual group. There were no significant differences between the transsexual and heterosexual group in mean serum LH concentration (6.9±2.4 U/l vs. 7.5±2.6 U/l), mean LH nadir interval (77±37 min vs. 70±16 min), and mean LH pulse amplitude (2.9±1.1 U/l vs. 3.0±1.1 U/l). Serum estrone, 17-β-estradiol, testosterone, progesterone and FSH concentrations also did not differ between the two groups. There also was not a higher prevalence of polycystic ovarian disease in our f-to-m transsexual group than in the general population.

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion.

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.

Serotonin involvement in the inhibition of luteinizing hormone (LH) release induced by prostaglandin D 2 (PGD 2) in castrated male rats

p-Chlorophenylalanine (PCPA, 320 mg/kg i.p.), an inhibitor of serotonin (5-HT) synthesis, and 5,6-dihydroxy-tryptamine (5,6-DHT, 50 μg i.c.v.), a drug toxic to the indoleaminergic system were used to test the involvement of 5-HT in the mediation of the inhibitory effect of prostaglandin D 2 (PGD 2) on luteinizing hormone (LH) release in castrated male rats. The i.c.v. administration of PGD 2 suppressed the episodic LH release characteristic of castrated rats and decreased mean plasma LH levels and mean LH pulse amplitude significantly. Pretreatment with PCPA or 5,6-DHT apparently eliminated the inhibitory effect of PGD 2 on LH secretion. These results suggest the possible involvement of a serotonergic mechanism in the mediation of the suppression of LH secretion induced by PGD 2 in castrated male rats.