Dynamics of bioactive luteinizing hormone-human chorionic gonadotropin during the first 7 days of life.

Serum luteinizing hormone-human chorionic gonadotropin bioactivity (B-LH) was measured daily in seven male and four female full-term newborns during the first 7 days of life. The B-LH levels were elevated in both sexes during the 1st day of life; subsequently, values decreased in both sexes. In males, they reached a nadir on the 4th day of life. A gradual secondary rise was then observed with B-LH levels on the 7th day significantly higher than on day 4 (p less than 0.025). By contrast, the B-LH levels in the females continued a gradual decline to levels significantly lower on day 7 as compared to day 4 (p less than 0.05). To determine whether pulsatile B-LH secretion occurs in newborns, serum concentrations were measured every 20 min for 2 h in eight male and seven female full-term neonates on the 7th day of life. Pulsatile secretion of B-LH was detected in six males and six females. This study demonstrates that pulsatility of gonadotropin secretion is characteristic of neonates as early as 7 days of life and that there is a dichotomy between the levels of B-LH in males and females; levels in females decline progressively from day 1 through 7, whereas in males, a nadir is reached on day 4 with a secondary rise developing thereafter. This male sex-specific rise is presumably the drive responsible for the characteristic postnatal increase in testosterone which peaks at 1 to 2 months of age.

A receptor-binding region in human choriogonadotropin/lutropin beta subunit.

Synthetic fragments have not been widely used thus far to evaluate structure-activity relations in the glycoprotein hormones. We prepared a series of peptides representing the intercysteine "loop" sequence (residues 38-57) in human choriogonadotropin (hCG) and lutropin (hLH) beta subunits, anticipating that it might be oriented toward the surface and accessible to receptors. The peptides were characterized chemically and tested for bioactivity by binding to rat ovarian membrane receptor and stimulation of Leydig cell testosterone production. The hCG beta-(38-57) and hLH beta-(38-57) peptides inhibited binding of 125I-labeled hCG half-maximally at 1.51 X 10(-4) and 2.03 X 10(-5) M, respectively, while other peptide hormones and fragments from elsewhere in the beta subunit were inactive. Both peptides stimulated testosterone production, with half-maximal responses at 3.55 X 10(-5) M (hCG) and 2.18 X 10(-5) M (hLH). By radioimmunoassay with an antibody to thyroglobulin-conjugated hCG beta-(38-57) peptide, native hCG and beta subunit were highly reactive, as were the reduced and carboxymethylated subunit and peptide. Helical-wheel projection predicted an amphipathic region in the N-terminal portion of the 38-57 sequence, and circular dichroic measurements showed an increase in ordered structure, especially alpha-helix, when the 38-57 peptides were transferred from an aqueous to a more lipophilic (90% trifluoroethanol) environment. These results indicate that the 38-57 region of beta subunit is exposed on the surface and constitutes a component in the receptor-binding domain for hCG and hLH. A region of amphipathic-helical structure in the 38-57 sequence may promote hormone-receptor interactions in a manner proposed for several other peptide hormones.

Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro.

The effects of LHRH and a potent LHRH agonist (LHRHa) on invitro testosterone production by enzyme-dispersed rat interstitial cells were evaluated. In a series of in vitro experiments, neither basal nor human menopausal gonadotropin (hMG)-stimulated testosterone production were significantly affected by doses of LHRH or LHRHa ranging from 10(-12)--10(-5) M. In addition, adult male rats were treated chronically with once daily injections of LHRH or LHRHa (2 micrograms/rat) or the vehicle for 1--7 days and decapitated 24 h after the last injection, and their testes were removed and weighed. Testicular weights decreased significantly by day 3 and were maximally decreased by day 6. In vitro testosterone production in response to 1--5 mIU human menopausal gonadotropin was markedly impaired (greater than 50%) in cells from rats treated with LHRHa for 2 days or longer and in rats treated with LHRH longer than 3 days. These data indicate that 1) LHRH and LHRHa do not alter in vitro testosterone production by dispersed rat interstitial cells and 2) interstitial cells of rats pretreated with LHRH and LHRHa exhibited impaired in vitro testosterone production. The data do not, however, rule out a direct effect of LHRH or LHRHa on testicular systems other than those involved in steroidogenesis.

Gonadotropin determinations in times 3-hour urine collections during the menstrual cycle and LHRH testing.

The usefulness of timed 3-hour urine collections as a substitute for serum gonadotropin (LH and FSH) determinations during the menstrual cycle and during LHRH testing was examined. The timing of the 3-hour urine collection is not important in mature individuals, since no significant temporal trend was found when aliquots were collected every 3 hours throughout two 24-hour periods in one mature woman. Good correlation was found between serum LH and FSH concentrations and the quantity of LH and FSH in timed 3-hour urine specimens throughout normal, ovulatory menstrual cycles in two women. Studies before and during 51 LHRH stimulation tests in normal men, children, and women during different phases of the menstrual cycle and in patients with a variety of hypothalamic-pituitary-gonadal axis disorders were performed. There was good correlation between the quantity of the gonadotropins in time 3-hour urine collections and the mean serum LH and FSH concentrations before and during the LHRH test. The "response area" for serum LH and FSH also correlated well with the amounts of LH and FSH in the urine collected during this period. Therefore, the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.

Gonadotropin determinations in timed 3-hour urine collections during the menstrual cycle and LHRH testing.

PIP: Gonadotropin determinations in timed 3-hour urine collections during the menstrual cycle and luteinizing hormone-releasing hormone (LHRH) testing are reported. No marked temporal trend was seen when urine aliquots were collected every 3 hours throughout 2 24-hour periods in 1 mature woman. A good correlation (p less than .001) was seen between serum LH and follicle stimulation hormone (FSH) concentrations and the quantity ovulatory menstrual cycles in 2 women. A good correlation (p less than .001) was also seen between the quantity of the gonadotropins in timed 3-hour urine collections and serum LH and FSH concentrations before and during the LHRH test in 51 normal men, women, and children and in patients with hypothalamic-pituitary-gonadal axis disorders. The "response area" for serum LH and FSH also correlated well (p less than .001) with the LH and FSH in the urine collected. It is concluded that the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.^ieng