Pulsatile Gonadotropin Secretion Research Articles

Pulsatile Gonadotropin Secretion Determined by Frequent Sampling from the Intercavernous Sinus of the Mare: Possible Modulatory Role of Progesterone during Luteolysis1

Twelve horse mares were used in a repeated-measures design consisting of 3 replicates of 4 mares each. On Day 6 following ovulation, luteolysis was initiated with an i.m. injection of prostaglandin F2 alpha (PGF2 alpha; Lutalyse, 10 mg). Either 12 (-12) or 36 (-36) h before PGF2 alpha (PRE), blood samples were collected simultaneously from the intercavernous sinus (ICS) and jugular (JUG) vein at 10-min intervals for an 8-h period. Pituitary capacity to exogenous GnRH (2 micrograms/kg BW, i.v.) was evaluated at the alternate time point within this period. Frequent sampling and GnRH challenge were repeated 36 (+36) or 60 (+60) h after PGF2 alpha (POST). Progesterone reached a nadir 48 h after PGF2 alpha, while the first significant elevation in estradiol (p < 0.05) was not detected until 156 h. PRE LH and FSH pulse frequencies in ICS samples were 0.6 +/- 0.3 and 1.8 +/- 0.8 pulses/8 h, respectively. Three high-amplitude, concurrent ICS pulses of LH and FSH were observed during this period. These were associated with elevated gonadotropin levels in the corresponding JUG samples. In contrast, low-amplitude ICS pulses at this time were predominately releases of FSH alone that were not detectable in the JUG. Following luteolysis, POST gonadotropin pulse frequencies in the ICS increased (p < 0.001) to 7.4 +/- 0.4 and 6.8 +/- 0.5 pulses/8 h for LH and FSH, respectively. Concurrent LH and FSH releases of relatively low amplitude characterized 87.7% of the POST ICS pulses, none of which were measurable in corresponding JUG samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Follicular development and reproductive endocrinology during a synchronized estrous cycle in heifers and mature cows displaying contrasting superovulatory responses

Ovarian follicular development and plasma concentrations of progesterone (P4), estradiol-17β (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared during a synchronized estrous cycle between heifers and mature cows displaying contrasting superovulatory responses. Six heifers <2 years old with a history of good responses to superovulatory (SOV) treatment and six cows 9 to 13 years old with poor responses to SOV treatments were used. Follicular development was monitored by daily ultrasonography. Blood samples were collected two to three times daily for P4 and E2 and thrice daily for LH and FSH analysis. Intensive sampling (samples every 15 min for 6 hr) was performed at critical periods of follicular development to analyze the pulsatile secretion of gonadotropins. In both cattle groups, a transient increase (P = 0.0001) in E2 occurred 4 to 5.7 d after the preovulatory LH surge or 2.3 d before the dominant follicle reached its maximum size. FSH concentrations increased (P = 0.006) before the emergence of the second cohort of follicles and then decreased despite no change in the concentration of E2. Contrary to our expectation and despite differences between groups in terms of age, number of previous SOV treatments, and divergent responses to superovulation, follicular development was similar in both groups. However, during the luteal phase, concentrations of E2 and FSH and LH pulse amplitudes were less (P ⩽ 0.05) in cows than in heifers. Therefore, follicular development monitored by ultrasonography and endocrine profiles during a synchronized estrous cycle are of limited value to predict quality of embryo donors.

Endogenous glutamate involvement in pulsatile secretion of gonadotropin- releasing hormone: evidence from effect of glutamine and developmental changes

The secretion of GnRH can be stimulated by glutamate (GLU) and GLU agonists, whereas GLU receptor antagonists inhibit GnRH. Using 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase, we aimed to study the involvement of endogenous GLU in GnRH secretion through the effects of impaired GLU biosynthesis from its precursor glutamine (GLN). GnRH secretion by hypothalamic explants of male rats, aged 15 and 50 days, was compared, because the frequency of spontaneous GnRH secretory pulses showed a 2-fold increase between those two ages. Using explants of 50-day-old rats, GLN elicited GnRH secretion in a similar dose-related manner as GLU. DON prevented GLN-evoked secretion of GnRH, whereas the effect of GLU was not altered. DON also markedly inhibited spontaneous pulsatile secretion of GnRH and the secretory response to veratridine, a Na+ channel opener. The inhibitory effect of DON on veratridine-evoked secretion of GnRH was directly related to the duration of exposure to DON and the frequency of GnRH secretory episodes. Using explants of 15-day-old rats, GLN could elicit GnRH release, although this response was lower than GLU-evoked secretion of GnRH. The DON concentrations required for inhibition of veratridine-evoked secretion of GnRH were lower at 15 days than at 50 days. These data indicate that 1) GLU biosynthesis from GLN is a prerequisite to the physiological mechanism of pulsatile GnRH secretion; and 2) inhibition of veratridine- or GLN-induced secretion of GnRH requires higher DON concentrations after the onset of puberty than before. This suggests that glutaminase, the enzyme controlling GLU biosynthesis from GLN, shows increased activity after the onset of puberty when the frequency of pulsatile GnRH secretion is increased as well.

A physiological role for N-methyl-D-aspartic acid and non-N-methyl-D- aspartic acid receptors in pulsatile gonadotropin secretion in the adult female rat

The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 micrograms/rat), a specific competitive NMDA receptor antagonist; 6,7-dinitroquinoxaline-2,3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, through LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.

A physiological role for N-methyl-D-aspartic acid and non-N-methyl-D-aspartic acid receptors in pulsatile gonadotropin secretion in the adult female rat.

The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 micrograms/rat), a specific competitive NMDA receptor antagonist; 6,7-dinitroquinoxaline-2,3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, through LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.

Abnormal Twenty-Four-Hour Pattern of Pulsatile Luteinizing Hormone Secretion and the Response to Naloxone in Women With Hyperprolactinaemic Amenorrhoea

Summary OBJECTIVE Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24-hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied. DESIGN The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10-minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1 6 mg per hour for 4 hours. PATIENTS Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle. MEASUREMENTS Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10-minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH. RESULTS The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean ± SEM 4.5 ± 2.4 vs 13.5 ± 2.5 vs 17 3±0 8, P<0 001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P<005) so the overall mean concentrations of LH throughout the 24-hour period was similar in the three groups (5 2±1 1, 4.8±0 8 and 5.2 ±0.4 U/I respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 μg every 90 minutes. CONCLUSIONS The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.

Release of gonadotropin-releasing hormone (GnRH) from the medio-basal hypothalamus induced by electroacupuncture in conscious female rabbits.

In electroacupuncture (EA) treatment, successful induction of ovulation is usually accompanied with the facilitation of pulsatile secretion of gonadotropin. The present work studied the release of GnRH from the mediobasal hypothalamus (MBH) using push-pull perfusion technique in conscious New Zealand female rabbits before, during and after EA stimulation. EA (4Hz, 5mA, 30 min) of Guanyuan (Ren 4), Zhongji (Ren 3), bilateral Sanyinjiao (SP 6) and Zigong (Extra 16) was given at the end of the 1st, 3rd and 5th hour during 6 hours' perfusion (EA group, n = 6). Cupric acetate (CuAC) was given (1%, 0.9 ml, i.v.) at the end of the 1st hour perfusion (CuAC group, n = 5) as a control since it is known as a stimulant for the release of GnRH. Rabbits in the control group (n = 4) were under the same perfusion condition except with no CuAC injection or EA stimulation. It was found that GnRH level was elevated immediately and significantly (4.64 +/- 0.98 v.s. 2.08 +/- 0.01 pg/ml, P < 0.05) after EA stimulation. In the CuAC group, GnRH level was also significantly elevated (3.84 +/- 0.37 v.s. 2.08 +/- 0.001 pg/ml, P < 0.05) one hour after CuAC injection. In addition, corpus lutein were observed both in the EA group (2/6) and the CuAC group (5/5). No similar changes were found in the control group. The data suggest that EA is capable of facilitating GnRH release from the MBH.

Autonomous gonadotropin release from the human pituitary in vitro and factors influencing this secretion.

Our understanding of the hypothalamus as the sole pacemaker for episodic hormone release has been challenged by recent observations of an autonomous rhythmic secretion from the pituitary, independent of hypothalamic inputs. Using an in vitro perifusion system, we were able to demonstrate an intrinsically pulsatile gonadotropin secretion from human fetal and adult pituitaries. This high-frequency/low-amplitude release is calcium-dependent and stimulated by gonadotropin releasing hormone (GnRH) administrations. Also, the autonomous release of luteinizing hormone (LH) appears to be temporally and functionally linked to the spontaneously pulsatile secretion of other anterior pituitary hormones, suggesting the existence of a common intrapituitary mechanism entraining these hormone pulsatilities. Further, the spontaneous and GnRH-stimulated LH release is greater from human female fetal pituitaries than from male fetal pituitaries at mid-gestation, presumably a reflection of differences in the negative feedback actions by factors from the fetal gonads. Collectively, we have observed an autonomous gonadotropin release from the human pituitary independent of, but facilitated by, GnRH. This spontaneous pulsatile secretion is calcium-dependent and entrained to the release of other anterior pituitary hormones. Therefore, it may represent the activity of a common intrapituitary pulse-generating mechanism and its modulation by factors from inside and outside the human pituitary.

The effect of flutamide on pulsatile gonadotrophin secretion in hyperandrogenaemic women.

The pulsatile gonadotrophin secretion in hyperandrogenaemic women was examined, following short-term androgen antagonism induced by flutamide, a specific androgen receptor blocker. Flutamide was administered to seven hyperandrogenaemic women and five normal cycling women, at a dose of 250 mg on the evening of day 1, followed by daily doses of 750 mg for 6 days. Blood samples were collected at 10 min intervals for 8 h before (day 1) and during treatment (days 2 and 6). Gonadotrophin and prolactin concentrations were measured in all samples while sex hormone concentrations were analysed in selected samples. Flutamide administration to hyperandrogenaemic women was followed by a decrease in luteinizing hormone (LH) pulse amplitude (P < 0.05), associated with an apparent decline in mean LH concentrations. Follicle stimulating hormone (FSH) showed a significant fall after 6 days of treatment (P < 0.05). Total testosterone, free testosterone, androstenedione and dihydroepiandrosterone sulphate were significantly decreased during flutamide administration, while sex-hormone-binding globulin and oestradiol were not affected. Normal women showed no significant changes in the above mentioned parameters. These results demonstrate that short-term androgen receptor blockade with flutamide reduces gonadotrophin secretion and androgen concentration in hyperandrogenaemic women. Since flutamide is devoid of intrinsic hormonal activity, it is suggested that the observed hormonal changes are secondary to the androgen blockade.

Abnormal twenty‐four hour pattern of pulsatile luteinizing hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea

Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24-hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied. The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10-minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1.6 mg per hour for 4 hours. Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle. Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10-minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH. The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean +/- SEM 4.5 +/- 2.4 vs 13.5 +/- 2.5 vs 17.3 +/- 0.8, P < 0.001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P < 0.05) so the overall mean concentrations of LH throughout the 24-hour period was similar in the three groups (5.2 +/- 1.1, 4.8 +/- 0.8 and 5.2 +/- 0.4 U/l respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 micrograms every 90 minutes. The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.

Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: Analysis of instantaneous secretion rate and secretory concomitance

International Journal of Gynecology & ObstetricsVolume 40, Issue 3 p. 271-271 Citations from the literature gynecological endocrinology Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: Analysis of instantaneous secretion rate and secretory concomitance P Inaudi, P InaudiSearch for more papers by this authorMJ Reymond, MJ ReymondSearch for more papers by this authorF Rey, F ReySearch for more papers by this authorAD Genazzani, AD GenazzaniSearch for more papers by this authorT Lemarchand-Beraud, T Lemarchand-BeraudSearch for more papers by this author P Inaudi, P InaudiSearch for more papers by this authorMJ Reymond, MJ ReymondSearch for more papers by this authorF Rey, F ReySearch for more papers by this authorAD Genazzani, AD GenazzaniSearch for more papers by this authorT Lemarchand-Beraud, T Lemarchand-BeraudSearch for more papers by this author First published: March 1993 https://doi.org/10.1016/0020-7292(93)90873-UAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume40, Issue3March 1993Pages 271-271 RelatedInformation

Evidence for attenuation of hypothalamic gonadotropin-releasing hormone (GnRH) impulse strength with preservation of GnRH pulse frequency in men with chronic renal failure.

To investigate the nature of putative disturbances in pulsatile gonadotropin (LH) secretion in men with chronic renal failure, we undertook blood sampling at 10-min intervals for 24 h in 9 hemodialysis-dependent uremic men and 16 community- and age-matched controls. Serum LH concentrations were measured in a 2-site immunoradiometric assay, which does not cross-react with free alpha or LH beta-subunit and correlates well with an in vitro Leydig cell bioassay. Deconvolution analysis was applied to calculate the number, amplitude, mass, and duration of spontaneous LH release episodes and simultaneously estimate the half-life of endogenous LH in each subject. We observed that: 1) the estimated half-life of immunoradiometric LH removal from plasma averaged 103 +/- 11 min in normal and 207 +/- 29 min in uremic men (P < 0.01); 2) the number of LH secretory bursts was slightly higher in uremic than healthy men (e.g. 20 +/- 2.2 vs. 15 +/- 1.0 secretory bursts/24 h, respectively; P = 0.05); 3) the mass of LH secreted per burst was approximately 50% lower in chronic renal failure than in health, namely 1.4 +/- 0.18 vs. 2.8 +/- 0.42 IU/L (P < 0.01); 4) the decrease in the mass of LH secreted per burst was not due to a decline in LH secretory burst amplitude, but rather an attenuation of LH secretory burst duration (4.8 +/- 0.35 min in uremic vs. 11 +/- 1.3 min in normal men; P < 0.001); 5) the mean 24-h serum immunoradiometric LH concentration was significantly higher in uremia at 5.7 +/- 0.68 vs. 3.6 +/- 0.41 IU/L in controls (P = 0.017); and 6) serum estradiol concentrations were increased in uremia, but total and free testosterone concentrations did not differ significantly between the two subject groups. In response to synthetic GnRH (10 micrograms, administered iv after the 24-h basal sampling period), the mean mass of immunoradiometric LH released within each calculated LH secretory burst was similar in uremic (n = 8) and normal (n = 21) individuals. We conclude that uremia is accompanied by a specific defect in the pulsatile mode of LH secretion, which is marked by an abbreviation of LH secretory burst duration and a consequent fall in the mass of LH secreted per spontaneous release episode. There is no overall decline in LH secretory pulse frequency or gonadotroph responsiveness to a submaximally effective dose of exogenous GnRH. Such findings are consistent with diminished hypothalamic GnRH impulse strength.(ABSTRACT TRUNCATED AT 400 WORDS)

The natural history of autonomous gonadal function, adrenarche, and central puberty in gonadotropin-independent precocious puberty.

Gonadotropin-independent precocity (GIP) is a syndrome marked by precocious pubertal development in the absence of pubertal levels of gonadotropins. To investigate the discrete patterns of central nervous system, gonadal, adrenal, and skeletal maturation in this syndrome, we conducted longitudinal studies spanning up to 10 yr in two such affected individuals. A cross-sectional analysis of adrenal androgen secretion was performed in nine additional patients to assess further the time course of adrenarche in GIP. Serial evaluations revealed progression of secondary sexual characteristics, statural growth, and skeletal maturation, all consistent with ongoing exposure to pubertal gonadal steroid levels. On the other hand, adrenarche (n = 11) and spontaneous and GnRH-stimulated gonadotropin secretion (n = 2) progressed in chronological age-appropriate manners despite long term pubertal levels of gonadal sex steroid secretion. After the development of central puberty, as documented by the appearance of pulsatile gonadotropin secretion, we sought to determine whether the potential for gonadal autonomy persisted. Despite complete pituitary desensitization induced by administration of a GnRH agonist, both patients studied demonstrated an ongoing capacity to secrete pubertal levels of gonadal steroids. Our study suggests that the timing of adrenarche and central puberty in these subjects with GIP was apparently unaltered by prolonged exposure to gonadal steroids. Subsequent to the development of central puberty, pulsatile gonadotropin secretion may override and, thus, mask the underlying defect(s) in adolescents and adults with histories of GIP.

Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: analysis of instantaneous secretion rate and secretory concomitance

To characterize the pulsatile secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) during the menstrual cycle and to statistically evaluate their secretory concomitance. Pulsatility study performed during the midfollicular and midluteal phases of a same menstrual cycle, blood samples being collected every 10 minutes for 6 hours. Participants investigated in the Division of Endocrinology, University Hospital. Nine healthy women (22 to 38 years) with regular menstrual cycles. Plasma LH, FSH, and PRL values were analyzed as raw and deconvoluted data, and the specific (nonrandom) secretory concomitance was evaluated statistically. The pulsatile secretion of LH was confirmed, and that of FSH and PRL was clearly established during both phases of the cycle by characterization of peak frequency, period, and amplitude. A specific secretory concomitance was assessed between LH and FSH in the follicular but not the luteal phase, and a tight concomitance between LH and PRL was demonstrated during both phases. These results are supportive of significant pulsatile secretions of the three hormones during the menstrual cycle, and they are demonstrative of a definite copulsatility of these hormones, suggestive of common regulatory factors in the complex temporal patterns of gonadotropin and PRL secretions along the cycle.

Pulsatile secretion of human chorionic gonadotropin (HCG) in early pregnancy

Pulsatile secretion of human chorionic gonadotropin (HCG) in early pregnancy

Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats.

The following study was conducted to examine the effects of estrogen and polypeptides, given either alone or in combination, on pulsatile gonadotropin secretion. One week after ovariectomy, rats received s.c. injections of oil or various doses (0.5, 5, 20 micrograms) of estradiol benzoate (EB) followed 1 day later by i.v. administration of 60 micrograms purified porcine follistatin, 10 micrograms recombinant inhibin, or the appropriate vehicle. Four hours after injection of the nonsteroids, blood was collected at 10-min intervals for 2 h, and the effects on pulsatile hormone release were assessed. Administration of EB alone dose-dependently suppressed mean and trough (lowest point between two pulses) FSH levels and all parameters of pulsatile LH release. Both follistatin and inhibin at the doses employed suppressed mean FSH levels to an equivalent extent (40%). Follistatin, but not inhibin, suppressed FSH pulse amplitude, while neither polypeptide alone influenced FSH pulse frequency or any parameter of pulsatile LH release. The effects of follistatin and EB on mean FSH levels were additive at all EB doses, whereas the effects of inhibin and EB were additive only at the middle EB dose. Follistatin in combination with the lowest EB dose significantly suppressed mean LH levels. These studies are the first to demonstrate that combined treatment with estrogen and the nonsteroids follistatin and inhibin is more efficacious in suppressing FSH release than treatment with either agent alone, thereby indicating that both steroids and nonsteroids are probably important in the physiological regulation of FSH secretion in rats. The additive effects of these compounds on FSH secretion could form the basis for exploring novel contraceptive interventions.

Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls

We studied 13 adolescents (mean gynecological age 29.2 +/- 14.1 months) with anovulatory cycles and 7 women with ovulatory cycles (mean gynecological age 33.1 +/- 15.3 months) as a control group. Adolescents with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 7) with high LH values, and group 2 (n = 6) with normal LH values. In all women plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied in each subject a second time 40 months later, to establish the outcome of the different pulsatile patterns. Group 1 had more frequent and greater LH pulses than the other two groups (which were similar) and had the highest plasma 17 beta estradiol, testosterone, androstenedione, and 17 hydroxyprogesterone concentrations. Longitudinal control showed that: in group 1, three subjects out of seven acquired ovulatory cycles and there was a fall in mean LH plasma levels (30 +/- 5 vs. 9 +/- 4 IU/L; P less than 0.01), number of pulses (8.3 +/- 1.5 vs. 5 +/- 0; P less than 0.025), mean amplitude (13 +/- 3 vs. 5 +/- 2 IU/L; P less than 0.02) and an increase in interpulse interval (56 +/- 10 vs. 91 +/- 6 min; P less than 0.01). In four subjects anovulatory cycles persisted and the LH pulsatile profile remained unchanged. In group 2, five subjects out of six acquired ovulatory cycles, but there were no significant changes in the number of pulses (6 +/- 1 vs. 6 +/- 2; P = NS), interpulse interval (97 +/- 30 vs. 85 +/- 30 min; P = NS), or amplitude (5 +/- 2 vs. 4 +/- 2 IU/L; P = NS). The results indicate that: 1) anovulatory young women with early normal plasma LH values have an adequate GnRh pulsatile pattern which will easily lead to ovulation; 2) anovulatory young women with high LH plasma values may have a reproductive system blocked in a pathological condition, similar to that observed in polycystic ovary syndrome; 3) only few subjects with high plasma LH values are able to achieve ovulation and normalize LH pulsatile pattern as a consequence of a new mode of GnRh release.

Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls.

We studied 13 adolescents (mean gynecological age 29.2 +/- 14.1 months) with anovulatory cycles and 7 women with ovulatory cycles (mean gynecological age 33.1 +/- 15.3 months) as a control group. Adolescents with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 7) with high LH values, and group 2 (n = 6) with normal LH values. In all women plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied in each subject a second time 40 months later, to establish the outcome of the different pulsatile patterns. Group 1 had more frequent and greater LH pulses than the other two groups (which were similar) and had the highest plasma 17 beta estradiol, testosterone, androstenedione, and 17 hydroxyprogesterone concentrations. Longitudinal control showed that: in group 1, three subjects out of seven acquired ovulatory cycles and there was a fall in mean LH plasma levels (30 +/- 5 vs. 9 +/- 4 IU/L; P less than 0.01), number of pulses (8.3 +/- 1.5 vs. 5 +/- 0; P less than 0.025), mean amplitude (13 +/- 3 vs. 5 +/- 2 IU/L; P less than 0.02) and an increase in interpulse interval (56 +/- 10 vs. 91 +/- 6 min; P less than 0.01). In four subjects anovulatory cycles persisted and the LH pulsatile profile remained unchanged. In group 2, five subjects out of six acquired ovulatory cycles, but there were no significant changes in the number of pulses (6 +/- 1 vs. 6 +/- 2; P = NS), interpulse interval (97 +/- 30 vs. 85 +/- 30 min; P = NS), or amplitude (5 +/- 2 vs. 4 +/- 2 IU/L; P = NS). The results indicate that: 1) anovulatory young women with early normal plasma LH values have an adequate GnRh pulsatile pattern which will easily lead to ovulation; 2) anovulatory young women with high LH plasma values may have a reproductive system blocked in a pathological condition, similar to that observed in polycystic ovary syndrome; 3) only few subjects with high plasma LH values are able to achieve ovulation and normalize LH pulsatile pattern as a consequence of a new mode of GnRh release.

Pulsatile gonadotropin secretion and basal prolactin levels during dopamine D-1 receptor stimulation in normal women

The effect of the specific dopamine D-1 receptor agonist Fenoldopam on pulsatile gonadotropin secretion and prolactin (PRL) secretion was investigated in normal women. The gonadotropin response to subsequent gonadotropin-releasing-hormone (GnRH) administration was also studied. Eight women received 8-hour infusions of either Fenoldopam (0.5 microgram/kg per minute) (Smith Kline and French, Harrow, United Kingdom) or placebo. After 7 hours of infusion, GnRH was given intravenously. The luteinizing hormone (LH) response to GnRH was significantly higher during Fenoldopam compared with placebo (LH; 13.1 +/- 9.0 versus 9.4 +/- 4.3 IU/L). Basal LH levels, pulse amplitude, and pulse frequency during Fenoldopam infusion were not different from placebo. Prolactin levels increased significantly during Fenoldopam (24 +/- 2 micrograms/L) compared with placebo (16 +/- 2). The results suggest that D-1 receptor stimulation does not affect pulsatile gonadotropin secretion but increases the pituitary responsiveness to GnRH. Additionally, dopamine and Fenoldopam have opposite effects on PRL secretion, the latter increasing PRL levels.

Patterns of Pulsatile Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Prepubertal (Midchildhood) Boys and Girls and Patients with Idiopathic Hypogonadotropic Hypogonadism (Kallmann's Syndrome): A Study Using an Ultrasensitive Time-Resolved Immunofluorometric Assay

To study the ontogeny of spontaneous pulsatile LH and FSH secretion before the onset of puberty, plasma LH and FSH were measured by an ultrasensitive time-resolved immunoflurometric assay in 16 boys and 6 girls, aged 6.5 +/- 0.2 yr (+/- SEM; range, 4.4-8.0) with short stature. Eight male patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome), aged 24.1 +/- 3.4 yr, were also investigated. Blood samples were withdrawn at 10- to 20-min intervals for 12 h from 2000-0800 h. Pituitary responsiveness was assessed by a standard iv LHRH challenge test. LH and/or FSH pulses were detectable in all but two prepubertal subjects. In boys, low amplitude LH (0.16 +/- 0.06 U/L) and FSH (0.19 +/- 0.03 U/L) pulses were detectable at mean frequencies of 2.19 +/- 0.37 and 2.13 +/- 0.46 pulses/12 h, respectively. In girls, low amplitude LH (0.29 +/- 0.18 U/L) pulses, but higher (P less than 0.05 compared to boys) amplitude FSH (1.62 +/- 1.05 U/L) pulses were observed at frequencies of 1.71 +/- 0.56 and 1.67 +/- 0.53 pulses/12 h, respectively. Mean FSH in prepubertal girls (1.95 +/- 0.88 U/L) was significantly (P less than 0.05) higher than that in boys (0.46 +/- 0.07 U/L), but mean LH was not different at 0.17 +/- 0.07 and 0.10 +/- 0.03 U/L, respectively. Patients with Kallmann's syndrome had mean LH and FSH levels indistinguishable from those of prepubertal boys. Nocturnal augmentation of pulsatile LH or FSH secretion was observed in 74% of children (71% in girls and 75% in boys), but in none of the eight patients with Kallmann's syndrome. A close temporal association was observed between sleep onset and the appearance of nocturnal pulsatile gonadotropin secretion. The FSH response to exogenous LHRH in prepubertal girls was significantly greater than that in patients with Kallmann's syndrome and prepubertal boys, but LH responses were not different. Our results show that pulsatile LH and FSH secretion occurs in the majority of boys and girls in midchildhood, with a robust association with nocturnal sleep onset. Between the ages of 4-8 yr, these low amplitude and low frequency pulses are unable to activate gonadal function. The regulation of FSH secretion in prepubertal girls appears to be different from that in prepubertal boys.(ABSTRACT TRUNCATED AT 400 WORDS)