Cortisol induction of growth hormone synthesis in a clonal line of rat pituitary tumor cells in culture.

Growth hormone synthesis increased markedly after addition of glucocorticoids at physiological concentrations to cultures of the GH(1) line of rat pituitary tumor cells. Stimulation of hormone protein synthesis by corticosteroids was selective, since (i) the rate of hormone synthesis increased while total protein synthesis decreased, and (ii) cortisol analogs, biologically inactive metabolites, and sex steroids did not induce growth hormone synthesis.

Persistent estrus and blockade of progesterone-induced LH release follows lesions which do not damage the suprachiasmatic nucleus.

Very small electrolytic lesions were made over the anterior or posterior portion of the optic chiasm in mature female rats showing normal estrous cycles. Lesions over the posterior portion of chiasm destroyed the suprachiasmatic nucleus of the hypothalamus (SCN) while the anterior lesions destroyed a small neural structure, here designated as the medial preoptic nucleus (MPN). Both lesions were effective in inducing persistent vaginal estrus, but when animals were ovariectomized and treated with exogenous and progesterone it was found that lesions including the MPN alone, but not the SCN alone, eliminated the positive feedback effects of this steroid regimen on LH release.

Effect of luteinizing hormone-releasing hormone on the secretion of luteinizing hormone, follicle-stimulating hormone, and testosterone in adult male rhesus monkeys.

Plasma levels of radioimmunoreactive LH, FSH, and testosterone (T) were assayed before and after administration of synthetic gonadotropin-releasing hormone (GnRH) to five chair-restrained rhesus monkeys with chronic indwelling venous catheters. Intravenous injection of 1, 5, and 25 microgram or infusion of 1 microgram/min for 25 min of GnRH resulted in a significant increase in plasma levels of LH. However, no significant increases in plasma FSH levels were detected. Plasma levels of T were also elevated after administration of 25 microgram GnRH, but peak concentration of T lagged behind peak levels of LH by approximately 30 min. These studies indicate that the male rhesus responds to GnRH administration by increased secretion of LH, followed by an increase in T levels. A concomitant increase in plasma FSH was not observed after treatment with GnRH in the doses used.

Developmental changes in the luteinizing hormone secretory pattern in peripubertal female rhesus monkeys: comparisons between gonadally intact and ovariectomized animals.

Developmental changes in LH release patterns were observed longitudinally in female rhesus monkeys at 10-65 months of age. The average ages of menarche and first ovulation in this experiment (n = 14) were 31.1 +/- 2.6 and 47.0 +/- 2.6 months (mean +/- SE), respectively. To assess the ovarian influence on developmental changes in LH, data were simultaneously obtained from neonatally ovariectomized animals at similar ages. The estimation of circulating LH was made with RIA as well as biological assay. During the prepubertal period (10-20 months of age), basal LH was very low, and there was no circadian fluctuation of LH in gonadally intact monkeys. During the early pubertal stage (20-30 months of age), before menarche, basal LH levels started to increase, and a circadian LH rhythm (nocturnal increases) appeared. At the midpubertal stage (30-50 months of age), a period between menarche and first ovulation, basal LH levels further increased, and the circadian LH rhythm was maximal. At the late pubertal stage (50-60 months of age), a period after the first ovulation during which the animals were not able to reproduce fully as adults, basal LH declined, and the circadian rhythm diminished. Similar but more exaggerated developmental changes in basal LH and the circadian fluctuation of LH were observed in females ovariectomized neonatally. Basal LH levels at 10-20 months were as low as those in intact animals with no circadian rhythm present. During the early pubertal period, a circadian fluctuation appeared at the time when a slight increase in the basal LH level occurred. Furthermore, the amplitude of circadian fluctuation (the difference between morning and evening LH values) increased linearly with the increase in basal LH during the midpubertal stage. These LH parameters in ovariectomized animals reached their peaks at 40-44 months, an age before the first ovulation in intact animals. As basal LH levels declined during the late pubertal stage to postpubertal stage, circadian fluctuation disappeared. The results suggest that the increase in LH output and concomitant circadian fluctuations occur in close association with the pubertal process, and this change in LH release is not dependent on the presence of the ovary. Therefore, we suggest that alteration of the LHRH release pattern during maturation, as reflected by LH release, rather than resetting of the gonadostat, is the key factor involved in the mechanism of the onset of puberty.

Pulsatile luteinizing hormone (LH) release during the progesterone-induced LH surge in the female rhesus monkey.

LH pulses during the progesterone (P)-induced LH surge were examined in ovariectomized and estrogen-treated female monkeys. Animals received a 2.5-mg P or oil injection 24 h after administration of 30 micrograms estradiol benzoate. The animals were fitted with jugular catheters connected to a tether-swivel system. Blood samples were collected at 10-min intervals starting 3-4 h before and ending 12-20 h after P or oil injection. Plasma LH was measured by both bioassay and RIA. LH pulses were determined by the PULSAR program. P administration induced a BIA-LH surge with a latency of 71 +/- 10 min in all seven animals. The P-induced bioassayable LH (BIA-LH) surge consisted of an ascending phase (204 +/- 24 min), a plateau period (174 +/- 32 min), and a descending phase (376 +/- 60 min). Oil injection did not cause a LH surge (n = 4). BIA-LH release before P and that during the P-induced LH surge were pulsatile. Pulse intervals of BIA-LH before P treatment (57.1 +/- 5.2 min) were not different from those before (55.0 +/- 11.7 min) and after (62.9 +/- 16.3 min) oil injection. In contrast, pulse intervals during the ascending phase (35.0 +/- 4.0 min), plateau period (34.6 +/- 2.6 min), and descending phase (45.0 +/- 3.1 min) were significantly shorter (P less than 0.02) than those before P. Pulse amplitudes of BIA-LH during the ascending phase (125.3 +/- 28.7 ng/ml) and plateau period (253.9 +/- 27.0 ng/ml) were significantly (P less than 0.001) higher than those (44.7 +/- 12.6 ng/ml) before P and during the descending phase (66.9 +/- 11.1 ng/ml). Radioimmunoassayable LH results were quite similar to those for BIA-LH, except that amplitude changes in radioimmunoassayable LH after P treatment were smaller than those in BIA-LH. It was concluded, therefore, that both the frequency and amplitude of pulsatile LH release increase during the P-induced LH surge, especially during the ascending phase and plateau period, in female rhesus monkeys. Furthermore, the present results support our previous conclusion that P facilitates pulsatile LHRH release with increases in frequency and amplitude in ovariectomized and estrogen-treated monkeys.

Increase in follicle stimulating hormone content occurs in cultured human fetal pituitary cells exposed to gonadotropin-releasing hormone.

To investigate the mechanisms by which GnRH regulates FSH production in the human fetus, dispersed pituitary cells from second trimester human fetuses were cultured on surface-modified plates. Exposure of cells to GnRH [(10(-8) and 10(-7) mol/L), study I] or [D-Ala6]des-Gly10-GnRH ethylamide (DALA) [(10(-11) to 10(-7) mol/L), study II] for 48 h resulted in an elevation of total FSH which correlated with an increase in releasable, but not nonreleasable, FSH. When pituitary cells were incubated for 24, 48 and 72 h with and without 10(-8) mol/L GnRH (study III), total FSH was significantly increased in cells cultured for 48-72 h without GnRH compared to cells lysed at the beginning of the incubation (p less than 0.001). At all intervals, GnRH significantly enhanced total FSH compared to respective controls (p less than 0.05).

Serum progesterone and corpus luteum function in pregnant pigtailed monkeys (Macaca nemestrina).

Corpus luteum (CL) function and control during pregnancy and early lactation in the pigtailed macaque was investigated. Peripheral concentrations of progesterone (P) on day 10 of pregnancy were 12.98 +/- 2.21 ng/ml and decreased progressively to 7.96 +/- 1.27 ng/ml by day 21 of pregnancy. The concentration of P increased around day 27 of gestation and reached peak levels of 18.48 +/- 2.45 ng/ml on day 37, thereafter gradually decreasing to a nadir at about midgestation. Ten days before parturition P concentrations increased again (P < 0.05). Concentrations of P decreased from 6.62 +/- 1.48 ng/ml on the day of delivery to 2.16 +/- 0.43 ng/ml on day 2 of lactation and remained low thereafter. Ovariectomy on day 35 did not affect the normal course of gestation or the patterns of P secretion during pregnancy. However, in these ovariectomized animals, in spite of suckling, P was not detectable after parturition. In intact monkeys, serum concentrations of P in the utero-ovarian vein at days 80 and 159 of pregnancy were higher relative to the uterine vein. Incubation studies utilizing 3H-cholesterol as a substrate revealed that the CL were capable of synthesizing P on days 35 and 159 of gestation. Histologically, the CL contained active luteal cells at late pregnancy. Low serum concentrations of chorionic gonadotropin were detected on day 10 of gestation; concentrations of this hormone reached high levels between days 18 and 24 and the titers were nondetectable after day 40 of pregnancy. Luteinizing hormone was present in constant amounts in the circulation during pregnancy and lactation. These data suggest that the CL of pregnancy in the pigtailed monkey is functional or capable of functioning during various stages of pregnancy. However, the fetoplacental unit is the primary source of P during the latter 4.5 months of gestation. As in other primates, a functional CL is not required for maintenance of pregnancy after implantation nor for lactation. Thus, the physiological significance of CL function during pregnancy is unclear.

Urinary gonadotropin and estrogen excretion during the postpartum estrus, conception, and pregnancy in the cotton-top tamarin (Saguinus oedipus oedipus).

Hormonal profiles during postpartum estrus, time of conception, and pregnancy were determined in urine samples from six cotton-top tamarins (Saguinus oedipus oedipus). Noninvasive collection techniques permitted daily sampling throughout lactation and pregnancy. Urinary estrone (E1), estradiol (E2), and both bioactive and immunoreactive luteinizing hormone/chorionic gonadotropin (LH/CG) measures revealed an interval of 19 ± 2.07 (S E M) days between parturition and the postpartum ovulatory LH peak. An increase in both E1 and E2 was seen prior to the LH peak; however, E1 and E2 continued to increase to their highest concentrations after the LH peak. Since postpartum ovulations resulted in pregnancy, neither postpartum estrus nor conception was suppressed by lactation. The length of gestation (measured from the LH peak to parturition) was 183.7 ± 1.14 (S E M) days, which is at least 30 days longer than that previously reported for other callitrichid species. Both E1 and E2 reached their maximum levels during midpregnancy but showed a rapid decline at parturition. Gestational levels of CG were first detectable approximately 20 days after the LH peak and continued to be elevated for approximately 80 days. The Sub-Human Primate Tube Test (SHPTT) for pregnancy did not detect the LH Peak and was less sensitive than other methods in detecting CG. Two RIA methods and a bioassay technique could not distinguish between LH and CG. We concluded that monitoring both estrogen and LH concentration was needed to determine when ovulation occurs in the cotton-top tamarin, since peak values of estrogen are seen after the ovulatory LH peak. Also, these tamarins were pregnant the majority of the time, indicating an unusually high fertility rate in contrast to most noncallitrichid primate species.