Mean Luteinizing Hormone Levels Research Articles

Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment

To determine if chronic treatment with the long-acting oral opioid antagonist naltrexone can increase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in women with secondary amenorrhea. Prospective. Large reproductive endocrinology unit of an academic hospital. Three groups of women with oligomenorrhea or amenorrhea: (1) hypothalamic amenorrhea; (2) anorexia nervosa; and (3) polycystic ovarian disease (PCOD). Naltrexone 50 mg every day for 4 days. Luteinizing hormone pulse pattern, frequency and amplitude, mean LH and FSH levels, measured by serial blood sampling over a 6-hour period before and after naltrexone. Naltrexone caused a significant increase (P less than 0.05) of the LH pulse frequency in patients with hypothalamic amenorrhea and in PCOD but not in anorexia nervosa. The mean levels of LH and FSH and LH pulse amplitudes were not significantly changed by naltrexone. The naltrexone nonresponders were underweight either because of simple weight loss or anorexia nervosa and had low levels of estradiol and an LH pulse pattern similar to the luteal one. The luteal LH pulse pattern in weight loss-related amenorrhea is caused by a nonopioid, undernutrition-linked factor.

Reversible, long-term inhibition of ovulation with a gonadotropin-releasing hormone antagonist in the marmoset monkey (Callithrix jacchus).

The effects of weekly injections of a gonadotropin-releasing hormone (GnRH) antagonist (GnRHa) ([N-acetyl-DβNal1-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8D-Ala10] NH2 GnRH) on pituitary and ovarian function were examined in the marmoset monkey, Callithrix jacchus. In experiment 1, five cyclic females were given weekly injections of vehicle (50% propylene glycol in saline) for 6 weeks followed by GnRHa for 20 weeks, animals receiving either 200 μg GnRHa/injection (n = 2) or 67 μg GnRHa/injection (n = 3) for 10 weeks, after which the treatment was reversed. Bioactive luteinizing hormone (LH) and progesterone (Po) were measured in blood samples (0.2-0.4 ml) collected twice weekly until at least 8 weeks after the last GnRHa injection. GnRHa treatment, timed to begin in the midluteal phase, caused a rapid decline in LH and Po and luteal regression after a single injection (both doses). Po levels were consistently low (<10 ng/ml), and ovulation was inhibited throughout 200 μg treatment in all animals. Short periods of elevated Po (>10 ng/ml) were, however, occasionally seen during 67 μg treatment, indicating incomplete ovarian suppression. Mean LH levels were significantly lower during GnRHa treatment compared with the period of vehicle injection (all animals 200 μg; three animals 67 μg), and there were significant differences in LH levels between GnRHa treatments (200 μg vs. 67 μg) in four animals. Four animals resumed normal ovarian cycles after the end of GnRHa treatment (15/16 days, three animals; 59 days, one animal); the fifth animal died of unknown causes 32 days after the last GnRHa injection. In a second experiment, pituitary responsiveness to exogenous GnRH was tested 1 day after a single injection of vehicle or antagonist (200 or 67 μg). Measurement of bioactive LH indicated that pituitary response to 200 ng native GnRH was significantly suppressed in animals receiving the antagonist, the degree of suppression being dose related. A third experiment examined the effect of four weekly injections of 200 μg GnRHa on follicular size and granulosa cell responsiveness to human follicle-stimulating hormone (hFSH) in vitro. Follicular development beyond 1 mm was inhibited by GnRHa treatment (preovulatory follicles normally 2-4 mm) although granulosa cell responsiveness to FSH during 48 hr of culture was not impaired. These results suggest that the GnRHa-induced suppression of follicular development and ovulation was mediated primarily by an inhibition of pituitary gonadotropin secretion and not by a direct action at the level of the ovary.

Modulation of pulsatile LH secretion by baclofen, a selective GABAB receptor agonist, in ovariectomized rats.

The effect of activation of central gamma-aminobutyric acidB (GABAB) receptors on pulsatile luteinizing hormone (LH) secretion was examined in unanesthetized ovariectomized rats. Intraventricular injections of 2 or 10 micrograms baclofen, a selective GABAB receptor agonist, usually arrested the existing pulsatile LH secretion for a short period, then LH pulses resumed with reduced frequencies and increased amplitudes. The increase in the pulse amplitude was not necessarily accompanied by a reduction in the pulse frequency, but was observed even after nonelongated interpulse intervals in animals receiving the GABA agonist. Mean LH levels showed complex bi- and triphasic fluctuations after the central administration of high and low doses of baclofen, respectively. It was concluded that central GABAB receptors are involved in the modulatory mechanism affecting the LH pulse frequency and amplitude in the ovariectomized rat.

Effects of Various Types of Hypothalamic Deafferentation on Luteinizing Hormone Pulses in Ovariectomized Rats

Abstract The pulsatile luteinizing hormone (LH) secretion in chronically ovariectomized rats bearing various types of hypothalamic deafferentation was examined. Ovariectomized rats were subjected to complete, anterolateral or anterior hypothalamic deafferentation and bled every 6 min for 3 h through an indwelling atrial cannula 5 days after the brain surgery. Another group of ovariectomized animals was subjected to posterior-anterior hypothalamic deafferentation (PAD), which cut off the anterior part of the arcuate nucleus from the mediobasal hypothalamus, and bled 1, 3 or 5 weeks after the deafferentation. Coronal sections of the brain were immunostained with anti-LH-releasing hormone (LHRH) serum. The pulsatile LH secretion was observed in rats bearing anterior, anterolateral or complete hypothalamic deafferentation and these types of deafferentation did not affect the frequency of LH pulses. The mean LH level during the 3-h sampling period and the amplitude of LH pulses decreased as the incision extended postero-laterally. Rats bearing PAD showed an irregular fluctuating pattern in plasma LH concentration 1 week after PAD. Parameters of LH pulses were restored with time after PAD. This suggests that the system generating LHRH pulses severed by PAD had been reorganized. LHRH-immunopositive neuronal fibres were found in the external layer of the median eminence in the rats bearing any type of deafferentation. The present results suggest that the frequency of LH pulses could be controlled by the LHRH pulse generator, which consists of non-LHRH neurons and is located in the mediobasal hypothalamus.

Gonadotropin pulsatility in a stimulated cycle: clomiphene citrate increases pulse amplitudes of both luteinizing hormone and follicle-stimulating hormone

To elucidate gonadotropin secretory patterns during ovarian hyperstimulation for in vitro fertilization. All volunteers who attended the unit during a period of 3 months were prospectively investigated. Infertility unit of the University Central Hospital of Oulu. Normally menstruating tubal infertility patients (n = 8) and healthy women with ovulatory cycles (hospital personnel, n = 11). All patients finished the study. Clomiphene citrate (CC), 50 mg, was administered on cycle days 5 to 9 and 300 IU of pure follicle-stimulating hormone (FSH) on cycle day 7 and 150 IU on cycle day 8. Serum samples for luteinizing hormone (LH) and FSH measurements were collected at 10-minute intervals for 6 hours on cycle day 7 (effect of CC) and day 9 (effect of CC/FSH), and the data were analyzed with the Munro computer program. The number of LH peaks was identical in the controls and study subjects on cycle days 7 and 9, whereas the pulse amplitude (P less than 0.025) and the pulse area (P less than 0.01) were higher in the CC/FSH-treated patients. The increase in overall mean LH level during the hormone therapy was not significant. In the CC/FSH-treated women, a decreased number of FSH pulses (P less than 0.01) with increased amplitude (P less than 0.001) and pulse area (P less than 0.01) was found. Clomiphene citrate treatment increased the mean FSH level (control versus cycle day 7, P less than 0.05) which was further increased (cycle day 7 versus cycle day 9, P less than 0.05) by FSH administration on cycle days 7 to 8. Otherwise pure FSH was found to be unable to modify endogenous LH or FSH secretory patterns under these conditions. Clomiphene citrate increases the amplitudes of both LH and FSH pulses in the midfollicular phase of a stimulated cycle, an effect which is not influenced by pure FSH administration.

Diurnal rhythm of testosterone and luteinizing hormone in hypogonadal men.

To determine the relationship between increasing luteinizing hormone (LH) production and the diurnal secretion of LH and testosterone (T) in adult men, studies were performed on five men with gonadotropin insufficiency associated with prolactinoma, five eugonadal men, and five men with primary testicular failure. Blood samples were drawn every 10 to 20 minutes for 24 hours beginning at 8:00 to 8:30 AM to evaluate diurnal periodicity. Mean (+/- SEM) LH levels in the three groups were 7.67 +/- 1.46 mlU/ml, 13.9 +/- 3.2 mlU/ml, and 62.3 +/- 14.4 mlU/ml, respectively, and mean serum T levels were 8.05 +/- 1.49 nmol/L, 13.9 +/- 3.5 nmol/L, and 9.15 +/- 1.3 nmol/L, respectively. Cosinor analysis revealed that each hyperprolactinemic man had a T rhythm with a significant 24-hour periodicity; the mean acrophase was at 5:00 AM. Testosterone levels were 35.0 +/- 10.6% less at 4:00 PM than at 8:00 AM. Eugonadal men also demonstrated a significant diurnal T rhythm with an acrophase at 6:00 AM, and T levels were 15.8 +/- 5.3% less at 4:00 PM than at 8:00 AM. By contrast, there was no significant diurnal rhythm in T secretion among the men with testicular failure, although serum T levels were 11.5 +/- 3.7% less at 4:00 PM than at 8:00 AM. For LH, hyperprolactinemic men demonstrated a significant 24-hour rhythm with an acrophase at 1:30 AM, whereas no significant 24-hour periodicity was identified among either eugonadal men or men with testicular failure.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of danazol on pulsatile gonadotropin secretion in women with endometriosis

To determine whether the effect of danazol on gonadotropin pulsatility was due to a direct effect of the drug or the suppression in the estradiol (E2) levels. Prospective analysis of serial blood samples at 10-minute intervals for 5 hours on days 3, 4, or 5 of the control cycle and 2 months after the start of danazol treatment. Tertiary institutional outpatient care. Six eugonadal women with minimal endometriosis. Oral administration of danazol, 200 mg three times daily. Gonadotropin mean levels, pulse frequency, and amplitude. The mean level of E2 was the same in the control cycle as that during danazol treatment (170 pmol/L). Danazol administration resulted in a 16% increase in the mean luteinizing hormone (LH) pulse amplitude (95% confidence interval [CI] 6% to 26%, P less than 0.01), associated with a 20% decrease in LH pulse frequency (95% CI -71% to +31%, P = 0.37). There was a nonsignificant increase in follicle-stimulating hormone (FSH) pulse amplitude (2%, 95% CI -9% to +14%, P = 0.68) and in FSH pulse frequency (27%, 95% CI -4% to +58%, P = 0.08). The 22% decrease in the mean LH level (95% CI -85% to +12%, P = 0.13) and the 20% decrease in the mean FSH level (95% CI -53% to +37%, P = 0.33) were also not significant. The increase in LH pulse amplitude represents a direct effect of danazol on the hypothalamic-pituitary axis.

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.

The luteinizing hormone pulsatile secretion: Diurnal excursions in normally cycling and postmenopausal women

While numerous investigations have determined characteristics of episodic luteinizing hormone (LH) secretion in women, any diurnal LH rhythmicities during eugonadal and hypogonadal states have not been accurately addressed. Accordingly, blood was sampled at 15-min intervals for 24 h in 45 normally cycling women (16 early follicular (EFP), 14 late follicular (LFP), 15 mid-luteal phase (MLP) women) and in eight postmenopausal women (PMW). Pulse attributes (amplitudes, interpulse intervals) determined in the LH secretory profiles were fitted to cosinor functions to assess diurnal variabilities. In both eugonadal women and PMW, significant (p less than 0.05 or less) diurnal excursions were observed in mean LH levels, with maximal acrophase amplitudes occurring in the EFP and MLP. While these 24-h swings peaked at comparable times (11.00-17.00) during the menstrual cycles, a significant (p less than 0.001) shift in acrophase times to early morning hours (05.30) was noted for PMW. Significant (p less than 0.05 or less) 24-h periodicities were also found for the LH pulse amplitudes. LH pulses were of greater magnitudes during night hours in both cycling women and PMW. A slowing of LH pulses (p less than 0.05 or less) was noted during sleep in EFP and, distinctly, in MLP women. These observations demonstrate diurnal variations in LH secretion and its pulsatile attributes in eugonadal women. Differences in time course and magnitude of these diurnal excursions may be explained by variations in the sex steroid environments. In turn, steroids may modulate other neuroendocrine determinants regulating central time-keepers.

Altered Neuroendocrine Regulation of Luteinizing Hormone Secretion in Postmenopausal Women with Parkinson’s Disease

The secretion of gonadotropins and the role exerted by the endogenous opioid system on luteinizing hormone (LH) secretion were investigated in 6 postmenopausal women affected by idiopathic Parkinson's disease (PD) as well as in 6 age- and weight-matched normal postmenopausal women as controls. The mean plasma follicle-stimulating hormone (FSH) and LH levels were evaluated both under basal conditions and after 20 days of conjugated estrogen administration (1.25 mg/day). At the same time, the activity of the endogenous opioid system was evaluated, as well as the LH response to the 4-hour infusion of the opioid antagonist naloxone (1.6 mg i.v. bolus followed by 1.6 mg/h). Both before and during estrogen administration, plasma FSH levels were similar in the two groups of subjects, whereas plasma LH levels were significantly lower (p less than 0.01) in parkinsonian than in control women. In each subject estrogen administration significantly blunted (p less than 0.01) plasma FSH levels. Plasma LH levels were reduced only in controls (p less than 0.05), but not in women with PD. In each subject, before estrogen administration, the plasma LH levels did not vary during naloxone infusion. In control women after 20 days of estrogen administration, the plasma LH levels significantly increased during naloxone infusion (p less than 0.01). By contrast, in women with PD, conjugated estrogens failed to restore the LH response to naloxone. The present results suggest that the neurotransmitter mechanisms, which regulate LH secretion, are altered, and, in particular, the activity of the endogenous opioid system is deficient in women with PD.

The Pulsatile Secretion of Gonadotropins and Growth Hormone, and the Biological Activity of Luteinizing Hormone in Men Acutely Intoxicated with Ethanol

The effects of acute alcohol ingestion were studied on pulsatile secretion of immunoreactive luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH), and on serum bioactive LH, testosterone, cortisol, and prolactin. A dose of 1.5 g ethanol per kg of body weight was administered by mouth to eight healthy male volunteers (aged 20 to 26 years) during 3 hr from 1800 to 2100 hr. Blood samples were collected every 20 min for 20 hr until 1400 hr of the following day. Each subject served as his own control in an identical experiment without ethanol, carried out at least 1 month later. Ethanol ingestion decreased serum testosterone concentration on average by 23% (p less than 0.05) between 10 and 16 hr after starting the drinking. The mean levels of LH and FSH and the mean number and amplitude of LH and FSH pulses remained unchanged. Ethanol ingestion did not affect the biological activity of LH. In each subject alcohol administration reduced the nightly peak of GH secretion, and in addition, changed the timing of this peak in most subjects. Only marginal changes were found in the prolactin levels but ethanol ingestion increased the cortisol levels on average by 36% (p less than 0.05) between 11 and 14 hr after the start of drinking. We conclude that the decrement in serum testosterone evoked by ethanol is not attributable to impaired pulsatile secretion of gonadotropins nor to reduced biological activity of LH. In contrast, ethanol profoundly suppressed the pulsatile secretion of growth hormone.

The Immunoreactive Inhibin Secretion Pattern In The Midluteal Phase: Relationships With Luteinizing Hormone And Progesterone

With the development of a sensitive radioimmunoassay for inhibin, luteal phase inhibin levels have been noted to parallel progesterone levels and be acutely dependent upon luteinizing hormone (LH) stimulation. To define the midluteal secretory pattern of immunoreactive inhibin and its relationships with LH and progesterone, blood samples were obtained from five normal women every 20 min for a period of 24 h. Individual data series of LH, progesterone and inhibin were analysed for pulsatile secretion using an adaptive-threshold method. Inhibin levels exhibited a relatively frequent, low-amplitude pulsatile secretory pattern (14.6 +/- 6.9 pulses/24 h (mean +/- SE), amplitude = 17% of the mean inhibin level). In contrast, LH levels demonstrated an infrequent high amplitude secretory pattern (6.2 +/- 0.7 pulses/24 h, amplitude = 139% of the mean LH level). The average progesterone pulse frequency and amplitude were intermediate to LH and inhibin (9.2 +/- 1.2 pulses/24 h, amplitude = 36% of the mean progesterone level). In addition, each individual's hormone data were analysed for coincident pulsatile secretion and cross-correlations were performed on the data, with one hormone pattern shifted relative to another by 20-min time intervals. None of the individual inhibin data series showed significant pulse coincidence when compared to the LH or progesterone data series. The cross-correlation analysis, however, revealed a significant (P less than 0.05) relationship in general trends between the inhibin and LH data series, and the inhibin and progesterone data series in three subjects.

Naloxone Affects the Luteinizing Hormone Secretory Pattern in the Short- and Long-Term Ovariectomized Rat

The effect of naloxone, an opiate receptor antagonist, on the secretory pattern of luteinizing hormone (LH) was evaluated in 4-, 16- and 32-week ovariectomized (OVX) rats. Freely moving rats bearing cardiac cannulae were bled every 6 min for 3 h. During the first 90 min of bleeding, an equal volume of saline was injected after withdrawal of each blood sample, while during the second 90 min the replacement was done with saline containing naloxone at a dose of 0.5 (lower dose) or 1.0 (higher dose) mg/kg/h; statistical comparison was done between both treatment periods. In 4-week OVX rats, a significant increase in the mean LH level was observed through the 90-min period of lower-dose naloxone treatment, without significant changes in the pulse frequency and amplitude. In 4-week OVX rats treated with the higher dose and in 16-week OVX rats treated with either the lower or the higher dose, a significant elevation in mean LH levels was observed only during the first 30 min of treatment, which was probably related to the first, large LH peak in the naloxone treatment period. However, together with pulses appearing later in the treatment period, no significant changes were found in the LH pulsatility except for a decrease in frequency in 4-week OVX rats. In 32-week OVX rats, even the lower-dose naloxone did not induce an elevation in mean LH levels. The results demonstrate that naloxone can increase the LH secretion in the absence of ovarian hormones, and further that the effect on LH changes depending upon the dose of naloxone and the time after ovariectomy.

Intracellular CA 2+ and excitatory amino acids in hippocampal neurons : Robert K.S. Wong, Department of Neurology, Columbia University, NY

Excitatory amino acid neurotransmission is an essential component of the neuroendocrine transmission line that regulates anterior pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Excitatory amino acids (EAAs), such as glutamate and aspartate, are found in largo concentrations in presynaptic boutons of a variety of important hypothalamic nuclei, including the arcuate nucleus, the suprachiasmatic nucleus, the supraoptic nucleus, the paraventricular nucleus, and the preoptic area. EAA receptors can be divided into two broad groups, namely, ionotropic and metabotropic receptors. Ionotropic receptors are subdivided into NMDA (N-methyl-D-aspartate), kainate, and AMPA (DL-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Their main mode of action is by the modulation of Na+, K+, and Ca2+ ion channels. Metabotropic receptors, on the other hand, act by a G-protein-stimulated release of intracellular Ca2+ or modulation of adenylate cyclase activity. The different EAA receptor subtypes are found in a variety of areas of the hypothalamus and the brain. In a variety of species, the administration of glutamate, NMDA, or kainate leads to LH release mediated through the stimulation of hypothalamic gonadotropin hormone-releasing hormone (GnRH) release. The major site of NMDA action appears to be the preoptic area—where GnRH cell bodies reside. AMPA and kainate appear to act primarily at the arcuate nucleus/median eminence, the site of GnRH nerve terminals. NMDA may also act upon noradrenergic neurons in the locus coeruleus to influence hypothalamic GnRH release. The steroid-induced LH surge in ovariectomized animals and the preovulatory surge of LH in cycling animals and in pregnant mare's serum gonadotropic-primed animals are blocked by the NMDA antagonist MK801 and the AMPA/kainate antagonist DNQX. MK801 also suppressed FSH surges in most instances, whereas DNQX had no effect on FSH surges. In the ovariectomized female rat, both the NMDA antagonist AP5 and the AMPA/kainate antagonist DNQX, lowered mean LH levels, LH pulse amplitude, and LH pulse frequency. Activation of NMDA receptors advanced the time of vaginal opening in the immature female rat, while kainate and DNQX were without effect. Gonadal steroid removal (castration) did not alter NMDA receptor levels or affinity in the hypothalamus of female or male rats. Likewise, steroid replacement to castrate rats did not affect hypothalamic NMDA receptor levels or NMDA R1 mRNA levels. Similarly, NMDA and kainate receptor levels in the hypothalamus did not change during the time of puberty in the female rat. In contrast, AMPA receptor (GluR1) immunoreactive levels in the magnocellular preoptic area (mPOA), the arcuate nucleus (ARC), and the suprachiasmatic nucleus (SCN) were found to be markedly elevated during the time of the LH surge in estradiol-progesterone-treated castrate rats compared to those of the vehicle-only-treated castrate rat. The release rates of glutamate and aspartate in the POA were found to be significantly elevated during the steroid-induced LH surge in the ovariectomized adult rat. Hence, the induction of the LH surge by steroids may involve enhanced EAA neurotransmission mediated by steroid-induced elevations in the release of glutamate and aspartate in the POA and AMPA receptors in the POA, the ARC, and the SCN. Evidence also exists supporting a role of EAAs in the release of other pituitary hormones, such as prolactin, ACTH, growth hormone, oxytocin, and vasopressin, as well as circadian rhythm induction and regulation. The above evidence points to a pivotal role of EAAs acting at the level of the hypothalamus in the neuroendocrine regulation of a variety of hormonal systems with the largest amount of data available on the control of gonadotropin secretion.

Effects of Lesions of the Suprachiasmatic and Paraventricular Nuclei on the Inhibition of Pulsatile Luteinizing Hormone Release by Exogenous Vasoactive Intestinal Peptide in the Ovariectomized Rat

Vasoactive intestinal peptide (VIP) inhibits pulsatile luteinizing hormone (LH) secretion in the ovariectomized rat. Hypothalamic nuclei known to contain VIPergic neurons were destroyed electrolytically to determine whether either an increased response or a loss of response to exogenous VIP would result. Bilateral electrolytic lesions were made of either the suprachiasmatic (SCN) or paraventricular (PVN) nuclei in separate experiments; all animals received an intracerebroventricular cannula at the same time. Sham-lesioned animals were used as a control. One week later, a catheter was placed in the jugular vein of each rat and, after a recovery period of at least 2 h, blood samples were taken every 5 min for 3 h. After a control period of 1.5 h, either VIP or saline was infused into the third ventricle for an additional 1.5 h. Two doses of VIP were used: 3.5 nmol/h, previously shown to be inhibitory, and 0.4 nmol/h, which is ineffective in ovariectomized rats. LH was measured in the plasma by radioimmunoassay. The high dose of VIP lowered mean LH levels and pulse frequency but had no effect on pulse amplitude in both sham-lesioned and SCN-lesioned rats. The low dose of VIP did not affect pulsatile LH patterns in sham-lesioned rats, but did lower mean LH and pulse frequency in SCN-lesioned rats, indicating a denervation hypersensitivity subsequent to SCN lesions. Destruction of the PVN abolished the inhibitory effect of the high dose of VIP on pulsatile LH release. The low dose of VIP was ineffective in both PVN- and sham-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.

Effects of clomiphene citrate on episodic luteinizing hormone secretion throughout the menstrual cycle

Pituitary luteinizing hormone secretory dynamics (pulse frequency and amplitude) were evaluated in eight normal women administered clomiphene citrate or placebo. After 5 days of treatment clomiphene citrate was found to increase mean luteinizing hormone secretion by increasing the amount of pituitary luteinizing hormone released per pulse. No change in pituitary luteinizing hormone interpulse interval was found in the follicular phase of the cycle, although a faster pulse frequency in the luteal phase was found after clomiphene citrate when compared with placebo. No differences were found in the luteal phase (pulse frequency, amplitude, and mean luteinizing hormone level) after clomiphene citrate versus placebo in the volunteers. These data suggest that the principal mechanism of action of clomiphene citrate is an increase in the concentration of hypothalamic gonadotropin releasing hormone into the hypothalamic-pituitary portal circulation, with a resultant increase in pituitary luteinizing hormone secretion.

Pulsatile Luteinizing Hormone Secretion in the Rat: Methodological Aspects of Cannulation Route and Sampling Intensity

Abstract We have investigated some requirements for valid estimates of pulsatile luteinizing hormone (LH) secretion in the castrate male rat. The choice of cannulation route and the minimal sampling intensity required to produce stable, unbiased estimates of parameters of pulsatile LH secretion were examined. Castrate mature male Wistar rats with unilateral ligation of a carotid artery (an inevitable consequence of carotid artery cannulation) had a 47% reduction in mean LH levels (1.8 vs 3.4 ng/ml, P< 0.011) attributable to a 40% reduction in LH pulse frequency (6.2 vs 10.4 peaks/6 h P<0.006) without change in LH pulse amplitude or other parameters of pulsatile LH secretion. In another study, a range of sampling intensities were examined to derive estimates of pulsatile LH secretion. Parameter estimates derived from the most intensive regime (q10 min sampling for 6 h) were compared with estimates of pulsatile LH secretion parameters determined from less intensive derivative sub-series composed of either fixed sampling frequency, but variable total study duration (i.e. the first 1, 2, 3, 4 and 5 h at 10 min intervals), or a fixed total study duration but variable sampling frequency. LH pulse frequency (or its inverse, interpulse interval) was quite sensitive to sampling intensity whereas pulse amplitude, maximum, minimum and overall mean LH were estimated accurately at even relatively low sampling intensity (q20 min for one h duration). Lower frequency sampling (q20 min) gave marked underestimates of LH pulse frequency (4.9 vs 10.4 peaks/6 h, P<0.05) compared with q10min sampling over a 6h study. These results indicated that for stable and unbiased estimates of pulsatile LH secretion in the castrate mature male rat it is necessary (but may not be sufficient) to (1) avoid carotid artery cannulation and (2) undertake blood sampling at intervals of not more than 10 min for at least 3 h.

Naloxone does not Affect the Luteinizing Hormone‐Releasing Hormone‐Induced Inhibition of Luteinizing Hormone Secretion in Sheep

Abstract Injection of luteinizing hormone-releasing hormone (21 pmol) into the third cerebral ventricle of long-term ovariectomized ewes caused a marked inhibition of luteinizing hormone secretion. Mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly when compared with the control responses to saline (50 mul). A notable characteristic of the response was the delayed and sustained nature of the luteinizing hormone-releasing hormone-induced inhibition. In the presence of the opioid antagonist naloxone (4 +/- 25 mg iv), the central administration of luteinizing hormone-releasing hormone still produced a marked inhibition of luteinizing hormone secretion. Again, mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly. When naloxone was injected iv, there was a significant rise in mean luteinizing hormone levels as a consequence of an increase in pulse frequency (in four out of five ewes) and a significant increase in luteinizing hormone pulse amplitude. In conclusion, these data suggest that central opioid pathways sensitive to blockade by naloxone are not involved in the luteinizing hormone-releasing hormone-induced inhibition of luteinizing hormone release. Furthermore, in the long-term ovariectomized ewe, endogenous opioid peptides exert a tonic inhibitory influence on luteinizing hormone-releasing hormone/luteinizing hormone secretion.

The Effect of Laparoscopic Multiple Punch Resection of the Ovary on Hypothalamo-Pituitary Axis in Polycystic Ovary Syndrome

SUMIOKI, HISAO; UTSUNOMYIYA, TAKAFUMI; MATSUOKA, KOUICHIROU; KORENAGA, MICHIO; KADOTA, TORU Author Information