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PubMed1986

Human chorionic gonadotropin reduces aromatizable androgens and aromatase activity in women stimulated by clomiphene citrate and human menopausal gonadotropin.

Periovulatory steroidal dynamics in women undergoing ovulation induction with clomiphene citrate and human menopausal gonadotropin were studied in 31 women with tubal blockage. Serum estradiol levels were significantly reduced 36 hours after human chorionic gonadotropin administration (from 1792 +/- 162 to 926 +/- 132 pg/ml, p less than 0.001). Peripheral levels of testosterone and androstenedione did not change during this periovulatory time. Progesterone and 17 alpha-hydroxyprogesterone, as anticipated, significantly increased with an early rise noted within the first 8 hours of human chorionic gonadotropin administration (p less than 0.001). A significant reduction of the ratios of the steroidal pairs 17 alpha-hydroxyprogesterone-progesterone (17 alpha-hydroxylase) and androstenedione-17 alpha-hydroxyprogesterone (17,20-desmolase) was observed after human chorionic gonadotropin injection (p less than 0.001). Aromatase activity appeared to be inhibited because of a significant reduction in the estradiol/testosterone ratio 34 to 36 hours after human chorionic gonadotropin administration. Thus human chorionic gonadotropin, which triggers ovulation in women treated by clomiphene citrate-human menopausal gonadotropin, appears to partially reduce aromatizable substrate as well as inhibit aromatase activity.

Adult↗

PubMed1990

Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs.

Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog.

Anovulation↗

PubMed1984

Effects of dopamine and norepinephrine on in vitro spontaneous and gonadotropin-releasing hormone-induced gonadotropin release by dispersed cells or fragments of the goldfish pituitary.

Enzymatically dispersed goldfish pituitary cells or freshly prepared goldfish pituitary fragments continue to secrete gonadotropin spontaneously in a column perifusion system. After the establishment of basal secretion rates, treatment of dispersed pituitary cells with 5 and 500 nM dopamine, or pituitary fragments with 50 and 100 nM dopamine, decreased the amount of gonadotropin released into the perifusate. Perifusion with 500 nM dopamine also abolished the gonadotropin-release response to a 10 nM solution of a luteinizing hormone-releasing hormone analogue in both perifusion systems. Perifusion of pituitary dispersed cells or fragment preparations obtained from sexually regressed goldfish with 50 nM norepinephrine consistently increased the amount of gonadotropin released into the perifusate. These results provide in vitro evidence for direct dopamine inhibition of spontaneous gonadotropin release, blockade by dopamine of gonadotropin-releasing hormone actions, and norepinephrine stimulation of gonadotropin secretion in goldfish.

Animals↗

PubMed1989

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization.

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.

Estradiol↗

PubMed1980

Diagnosis of gonadotropin deficiency in adolescents: limited usefulness of a standard gonadotropin-releasing hormone test in obese boys.

The pubertal maturation of five boys (Group A) who were initially thought to be gonadotropin deficient was studied over 10 to 58 months (mean 36 months) by serial physical examinatons and standard GnRH tests. Four were seen because of obesity, delayed sexual maturation, depression, and poor school performance. The other boy had acquired hypothalamic hypopituitarism at 13 years of age. Gonadotropin responses during the initial GnRH test were either absent or abnormally low as related to the degree of skeletal maturation. Subsequent responses showed progressive maturation into the normal range for adult males. These boys had normal olfaction and moderate-to-marked obesity, but initial assessment of testicular size, basal gonadotropins, and testosterone or gonadotropin responses to GnRH did not distinguish these boys from seven patients with isolated gonadotropin deficiency (Group B). Contrary to previous reports and expectations, these studies indicate that an absent or markedly blunted response to synthetic GnRH is not diagnostic of gonadotropin deficiency, even when skeletal age is 12 years or greater. Furthermore, unless a patient is hyposomic or anosmic, or has an associated anomaly such as cleft palate, isolated gonadotropin deficiency cannot be diagnosed reliably until late adolescence or early adulthood.

Adolescent↗

PubMed2003

Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin-releasing hormone.

Gonadotropin-releasing hormone (GnRH) regulates reproduction in all vertebrates. Until recently, an antagonistic neuropeptide for gonadotropin was unknown. The discovery of an RFamide peptide in quail that inhibits gonadotropin release in vitro raised the possibility of direct hypothalamic inhibition of gonadotropin release. This peptide has now been named gonadotropin-inhibitory hormone (GnIH). We investigated GnIH presence in the hypothalamus of two seasonally breeding songbird species, house sparrows (Passer domesticus) and song sparrows (Melospiza melodia). Using immunocytochemistry (ICC), GnIH-containing neurones were localized in both species in the paraventricular nucleus, with GnIH-containing fibres visible in multiple brain locations, including the median eminence and brainstem. Double-label ICC with light microscopy and fluorescent ICC with confocal microscopy indicate a high probability of colocalization of GnIH with GnRH neurones and fibres within the avian brain. It is plausible that GnIH could be acting at the level of the hypothalamus to regulate gonadotropin release as well as at the pituitary gland. In a photoperiod manipulation experiment, GnIH-containing neurones were larger in birds at the termination of the breeding season than at other times, consistent with a role for this neuropeptide in the regulation of seasonal breeding. We have yet to elucidate the dynamics of GnIH synthesis and release at different times of year, but the data imply temporal regulation of this peptide. In summary, GnIH has the potential to regulate gonadotropin release at more than one level, and its distribution is suggestive of multiple regulatory functions in the central nervous system.

Animals↗

PubMed2005

Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail.

Until recently, any neuropeptide that directly inhibits gonadotropin secretion had not been identified. We recently identified a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of gonadotropin release is mediated by a novel G protein-coupled receptor in the quail pituitary. This new gonadotropin inhibitory system is considered to be a widespread property of birds and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To understand the physiological role(s) of GnIH in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in male quail. Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs in a dose-dependent manner. Plasma LH and testosterone concentrations were also decreased dose dependently. Furthermore, administration of GnIH to mature birds induced testicular apoptosis and decreased spermatogenic activity in the testis. In immature birds, daily administration of GnIH for 2 wk suppressed normal testicular growth and rise in plasma testosterone concentrations. An inhibition of juvenile molt also occurred after GnIH administration. These results indicate that GnIH inhibits gonadal development and maintenance through the decrease in gonadotropin synthesis and release. GnIH may explain the phenomenon of photoperiod-induced gonadal regression before an observable decline in hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified hypothalamic neuropeptide inhibiting reproductive function in any vertebrate class.

Animals↗

PubMed1983

Pituitary gonadotropin-releasing hormone receptors during gonadotropin surges in ovariectomized-estradiol-treated rats.

In intact cycling rats, the number of pituitary GnRH receptors varies markedly during the estrous cycle. Concentrations are maximal on diestrus and early proestrus, before falling rapidly for a brief period immediately before the preovulatory gonadotropin surge. In this study we investigated whether dynamic changes in ovarian steroids, pituitary hormones, and GnRH itself, all of which are changing at the time of the surge, play a role in the acute transient down-regulation of the pituitary GnRH receptors. We used the ovariectomized-estradiol-treated female rat as a model, as these animals exhibit daily gonadotropin surges at a predictable time of the day and also allow studies in a situation where concentrations of ovarian steroids are stable. The pituitary GnRH binding capacity (GnRH-BC) was measured using the analog D-Ala6des Gly10-GnRH ethylamide as ligand. GnRH-BC was stable between 0900-1530 h [range, 288 +/- 29 to 262 +/- 33 fmol protein (mean +/- SE)] and fell abruptly to 123 +/- 17 fmol/mg at 1630 h, before returning to the initial level by 1730 h. This abrupt fall in GnRH-BC preceded the afternoon gonadotropin surge and was similar in timing, magnitude, and duration to that observed in intact cycling rats. Serum PRL decreased from peak levels at 1630 h, coincident with the fall in GnRH-BC, before rebounding at 1730 h. Pentobarbital given at 1400 h abolished both the gonadotropin surge and the acute fall in GnRH-BC, but did not change serum PRL levels, suggesting that PRL is not causally related to the fall in GnRH-BC. The stable morning levels of GnRH-BC were not reduced after iv injections of LH, FSH, or both hormones despite elevations in serum gonadotropins to concentrations greater than those seen during the afternoon surge. Additionally, multiple iv injections of GnRH at 30- or 10-min intervals did not decrease the stable morning levels of GnRH-BC, although serum LH and FSH were markedly elevated. The data suggest that dynamic fluctuations in ovarian steroids, gonadotropins, PRL, and GnRH are not causally related to the acute transient reduction of pituitary GnRH receptors before the afternoon gonadotropin surge. These results also suggest that another hypothalamic or pituitary factor(s) is involved in the acute regulation of GnRH receptors, and the ovariectomized-estradiol-treated rat appears to be a good model for the elucidation of the factor(s) involved.

Animals↗

PubMed1988

Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease: a new approach to induction of ovulation.

A combined regimen based on exogenous gonadotropins followed by pulsatile gonadotropin-releasing hormone was attempted in order to induce ovulation in a group of patients with polycystic ovarian disease. The women were selected on the basis of previous unsuccessful treatment with clomiphene citrate, gonadotropin and pulsatile gonadotropin-releasing hormone used separately. At our first attempt at application of this new approach, in all patients follicular growth was recorded and ovulation was induced with exogenous chorionic gonadotropin, without hyperstimulation. Two clinical pregnancies were established. Retrospective hormonal evaluation showed the presence of two premature luteinizations. Pulsatile gonadotropin-releasing hormone administration following follicular recruitment with exogenous gonadotropin may therefore be considered an effective therapy for polycystic ovarian patients resistant to conventional treatment.

Adult↗

PubMed1986

Inhibition of gonadotropin secretion in castrated male rhesus monkeys (Macaca mulatta) induced by dietary restriction: analogy with the prepubertal hiatus of gonadotropin release.

The purpose of this study was to examine further the notion that in higher primates, analogous neuroendocrine mechanisms may underlie the hiatus in LH and FSH secretion during prepubertal development and the suppression of gonadotropin release in adults during states of malnutrition. To this end, the metabolic sequelae and the gonadotropin response to restricted food intake (RFI) were determined in nine castrated male rhesus monkeys. The results obtained were then evaluated in light of current understanding of the neuroendocrine bases of the ontogeny of gonadotropin secretion in primates. A reduction in food intake from approximately 1150 Cal/day to approximately 200 Cal/day for 20-34 days resulted in declines in body weight and circulating LH and FSH concentrations. The reduction in body weight and the suppression of LH secretion were statistically significant (P less than 0.05). The decrease in gonadotropin secretion induced by RFI was fully restored by the chronic iv intermittent infusion of GnRH (0.1 microgram/min for 3 min every hour). These findings graphically demonstrate that RFI, or a sequelae of this nutritional perturbation, inhibits gonadotropin secretion, in the absence of feedback influences by gonadal hormones, by an action at a suprapituitary level that is mediated by interruption of intermittent hypothalamic GnRH discharge. The apparent arrest of the neural mechanism that governs the timing of intermittent GnRH discharge, the so-called GnRH pulse generator, was associated with decreases in plasma insulin (P = 0.078), T4 (P less than 0.05), and T3 (P less than 0.05) concentrations and with a significant (P less than 0.05) elevation in circulating cortisol levels. Although a general decrease in circulating amino acid levels was not observed during RFI, plasma glutamate concentrations were significantly (P less than 0.05) reduced by the nutritional perturbation. RFI resulted in unremarkable hypoglycemia. While the suppression of gonadotropin secretion in castrated male monkeys during RFI resembled, in certain aspects, the hiatus in gonadotropin secretion during prepubertal development, the endocrine and metabolic concomitants of these two physiological states exhibited important differences. Thus, the contemporary notion that the study of dietary restriction in adult primates may provide insights into the neuroendocrine mechanisms that govern the timing of the onset of puberty in these species should not be accepted without careful consideration.

Amino Acids↗

PubMed1991

Inhibition of pituitary gonadotropin secretion by the gonadotropin-releasing hormone antagonist antide. I. In vitro studies on mechanism of action.

The GnRH antagonist antide is among the most promising "third generation" compounds available for clinical evaluation. In primates, antide manifests prolonged (several weeks) and reversible inhibition of pituitary gonadotropin secretion after a single high dose injection. In the present study, we have examined the effects of antide on pituitary gonadotropin secretion in vitro. Dispersed anterior pituitary cells from adult female rats were plated (48 h; 5 x 10(5) cells/well), washed, and exposed to increasing concentrations of antide for up to 48 h. Media were removed, and cells were washed twice and then incubated with GnRH (1 x 10(-8) M) plus antide for 4 h. Media and cell lysates were assayed for LH/FSH by RIA. Antide had no effect on basal LH/FSH secretion at any dose tested (10(-6)-10(-12) M). In contrast, GnRH-stimulated LH/FSH secretion was inhibited by this GnRH antagonist in a dose- and time-dependent manner. When incubated simultaneously, antide blocked GnRH-stimulated gonadotropin secretion, with a maximal effect at 10(-6) M (ED50, 10(-7) M). Preincubation of pituitary cells with antide for 6-48 h before GnRH exposure shifted the dose-response curve to the left; the maximally effective dose was 10(-8) M; the ED50 was 10(-10) M antide after 48-h preincubation. Intracellular LH/FSH levels increased concomitant with the decrease in secreted gonadotropins. Total LH/FSH levels (secreted plus cell content) remained unchanged. The inhibition of LH secretion by antide was specific for GnRH-stimulated gonadotropin secretion; antide had no effect on K(+)-stimulated LH secretion. Moreover, antide had little or no residual effect on LH secretion; full recovery of GnRH responsiveness in vitro occurred within 4 h after removal of antide. Lineweaver-Burke analysis of antide inhibition of GnRH-stimulated LH secretion indicated that antide is a direct competitor of GnRH at the level of the pituitary GnRH receptor. In summary, antide is a pure antagonist of GnRH stimulation of gonadotropin secretion; no agonistic actions of antide were manifest in vitro. Moreover, antide has no apparent noxious or toxic effect on pituitary cells in culture; the actions of antide are immediately reversible upon removal of antide from pituitary gonadotropes. We conclude that the long term inhibition of gonadotropin secretion by antide in vivo is not due to deleterious effects of this compound at the level of the pituitary gonadotrope.

Animals↗

PubMed1984

Serum gonadotropins after gonadotropin-releasing hormone injection in bulls subjected to spacial restriction.

Response patterns of luteinizing hormone, follicle-stimulating hormone, and testosterone after injection of gonadotropin-releasing hormone were investigated in bulls grouped by weight (250 to 459 kg body weight) and confined five per pen in 9.2 or 6.4 m2 space per bull in two replicates. Blood samples were collected for 1 h prior to injection of 100 micrograms gonadotropin releasing hormone and 5 h after injection at 15-min intervals. Overall mean luteinizing hormone concentrations were not affected by spacial restriction or replicate. Interaction of treatment by time revealed that luteinizing hormone response curves were not similar. Restricted bulls had a higher response of luteinizing hormone to gonadotropin-releasing hormone. Follicle-stimulating hormone increased in all groups within 15 min and peaked at 219.4 ng/ml at 45 min. Both gonadotropin responses returned to preinjection concentrations by 4 h. Testosterone was affected by treatment, replicate, and time of sampling. Testosterone was higher in restricted bulls and higher in replicate 2. Mean testosterone peak following gonadotropin-releasing hormone was 3.86 ng/ml and occurred between 105 and 120 min which was approximately 90 min after the gonadotropin peaks. It appears that hormone responses to gonadotropin-releasing hormone were not depressed by spacial restriction, and additional spacial restriction of young bulls could be used commercially.

Age Factors↗

PubMed2000

Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty.

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.

Adolescent↗

PubMed1986

The dependency of folliculogenesis and corpus luteum function on pulsatile gonadotropin secretion in cycling women using a gonadotropin-releasing hormone antagonist as a probe.

A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion.

Adult↗

PubMed1993

The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies.

To evaluate the effect of growth hormone on testicular response to human chorionic gonadotropins (hCG) in vivo in humans, we selected patients with combined deficits of GH and gonadotropins who were in substitution treatment with both GH (from the time of diagnosis) and gonadotropins (from the time of induction of puberty). Testicular response to gonadotropin therapy was then evaluated during and six months after the cessation of GH treatment. Blood samples were collected before and 2, 4 and 6 days after hCG administration. hCG responses were calculated and expressed as the areas under the response curve. We studied four hypogonadotropic patients (aged 18-19 years) with associated GH deficiency. Their gonadotropin treatment consisted of hCG 1,500 IU every six days, and FSH 75 IU every three days. The GH therapy replacement consisted of 4 IU thrice weekly. Testosterone, androstenedione, 17 alpha-hydroxyprogesterone and estradiol were measured. In all subjects the testosterone area during GH treatment was significantly higher compared to the testosterone area obtained without GH administration (2993 +/- 1091 vs 2310 +/- 751; M +/- SD; p < 0.04). The androstenedione area followed a similar pattern (708 +/- 377 vs 402 +/- 248; M +/- SD; p < 0.05). The 17 alpha-hydroxyprogesterone area, on the contrary, was significantly higher during GH withdrawal (542 +/- 307 vs 235 +/- 190; M +/- SD; p < 0.05). As far as the estradiol area is concerned, no significant differences were found (22,860 +/- 10,082 vs 25,697 +/- 13,640; M +/- SD). In conclusion, GH administration seems to improve testosterone production induced by human chorionic gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1989

A comparison of the suppressive effects of testosterone and a potent new gonadotropin-releasing hormone antagonist on gonadotropin and inhibin levels in normal men.

GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Na1-Glu [AcD2NaL1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 micrograms/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Na1-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1-2 days of Na1-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Na1-Glu administration. The combination of Na1-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Na1-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Na1-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.

Adult↗

PubMed1990

Acute inhibitory effect of follicle-stimulating hormone-suppressing protein (FSP) on gonadotropin-releasing hormone-stimulated gonadotropin secretion in cultured rat anterior pituitary cells.

Follicle-stimulating hormone (FSH)-suppressing protein (FSP) or follistatin, a novel gonadal glycoprotein hormone, has been shown to have chronic inhibitory effects on the secretion of both FSH and luteinizing hormone (LH) in response to gonadotropin-releasing hormone (GnRH) in vitro. The present study was designed to investigate the acute effects of bovine FSP on GnRH-stimulated gonadotropin secretion and to examine the potential subcellular sites of this action of FSP using cultured pituitary cells. Anterior pituitaries from adult male Sprague-Dawley rats were enzymatically dispersed and cultured for 48 h, after which the cells were treated with bovine FSP for 6 h, followed by a 4 h stimulation with secretagogues in the continued presence of FSP. Results showed that the 35 kDa form of bovine FSP (0.1-3 nM) dose-dependently suppressed GnRH-stimulated FSH and LH secretion, with inhibition of 38 and 25%, respectively, at 3 nM. In addition, FSP suppressed gonadotropin secretion in response to activators of protein kinase C (phorbol 12-myristate 13-acetate (PMA) and mezerein) and a calcium ionophore (A23187). However, FSP had no effect on gonadotropin secretion evoked by melittin, an activator of phospholipase A2. Furthermore, 35 kDa bovine FSP did not compete with GnRH for GnRH binding sites in a direct competition study and treatment of cultured pituitary cells with FSP (0.1-3 nM) for 10 h did not alter the number of GnRH binding sites on the cell membranes. Finally, similar inhibitory effects on gonadotropin secretion in response to GnRH, PMA and mezerein were obtained with the 31 and 39 kDa forms of bovine FSP, each at a concentration of 1 nM. We conclude from the present study that FSP acutely inhibits GnRH-stimulated gonadotropin secretion in cultured pituitary cells, and that FSP exerts its action beyond the GnRH receptor, possibly by affecting the protein kinase C and/or the calcium-calmodulin systems.

Animals↗

PubMed1988

Comparison of pulsatile subcutaneous gonadotropin-releasing hormone and exogenous gonadotropins in the treatment of men with isolated hypogonadotropic hypogonadism.

Eight men with isolated hypogonadotropic hypogonadism were treated with pulsatile gonadotropin-releasing hormone (GnRH) after maximal testicular growth and function had already been achieved with human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Only four subjects could normalize plasma testosterone (T) levels (group A). After 18 months of GnRH therapy, testicular size of group A increased by 53% (P less than 0.01) over that previously attained with exogenous gonadotropins. However, despite further testicular growth, two men who were previously azoospermic on hCG/hMG remained so on GnRH. In the other two patients, total sperm count increased minimally. Thus, pulsatile gonadotropin levels achieved with GnRH are more effective in stimulating testicular growth, but not necessarily sperm output, than are stable gonadotropin concentrations obtained with hCG/hMG.

Adult↗