Estradiol and progesterone effects on relative luteinizing hormone and follicle stimulating hormone release induced from superfused anterior pituitary cell cultures by defined LHRH pulse regimens

Abstract

These studies examined the capacity of estradiol and progesterone to modulate relative luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from superfused anterior pituitary cells when stimulated with luteinizing hormone releasing hormone (LHRH) pulse regimens of specific amplitude, duration and frequency. There was particular interest in whether such steroid and LHRH treatments induced evidence of divergent LH or FSH secretion. Pituitaries were recovered from adult, 2 week ovariectomized rats and cultured for 48 h with collagen coated Cytodex microcarrier beads. Cultures were preincubated either with or without estradiol (1 or 10 nM) for 48 h and were subsequently incubated for 3, 6 or 12 h with 100 nM progesterone. All groups were then pulsed with 1 of 3 LHRH regimens; regimen 1 delivered 8 ng in a single 100 μl bolus once/h; regimen 2 divided the 8 ng dose of regimen 1 into 3 equal doses administered at 4 min intervals thereby maintaining the 8 ng mass of regimen 1 while extending the duration of exposure; regimen 3 was the same as regimen 2 except that the 3 equal doses were administered at a pulse frequency of 1 per 2 h rather than 1 per h thereby not only maintaining the duration of exposure as in regimen 2 but also reducing the pulse frequency. 1 nM estrogen alone for 48 h had no effect on LHRH stimulated LH release regardless of regimen; however, FSH was increased when hourly pulses of increased duration were applied (regimen 2). When estrogen was increased to 10 nM, regardless of regimen, LH was predominantly inhibited while FSH was unaffected. When 1 nM estrogen was followed by progesterone, both LH and FSH were elevated at 6 h progesterone in response to regimen 2; with 10 nM estrogen however, a divergent response was observed in that LH release was elevated at 6 h while FSH was elevated at 3 h in response to regimens 2 and 3. These results first of all confirm that progesterone in combination with estrogen is capable of exerting both inhibitory and stimulatory effects on gonadotropin secretion; secondly, these studies show that, as a direct pituitary effect, the LHRH regimen and the gonadal steroid milieu are capable of interacting to significantly influence the relative secretion of LH and FSH. The data therefore suggest that the divergent gonadotropin secretion seen in various physiological states in vivo is due likely in part to a combination of estrogen and progesterone priming in combination with the hypothalamic LHRH secretory pattern.