Biphasic Effect of Estrogen on the Sensitivity of the Pituitary to Luteinizing Hormone-Releasing Factor (LRF)

Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

“…Moreover, by day 5 of estradiol replacement, the increment of peak 2 over peak 1 nadir was significantly greater than the increment of peak 1 over basal (P < 0.025). This augmentation ofthe peak 2 amplitude occurred to a lesser and insignificant degree on days 10 replacement. A generally similar pattern relating peak 2 and peak 1 was observed in relation to estradiol replacement when peak amplitudes were expressed as percentage increases (right panel of Fig.…”

“…Investigations in ovariectomized rodents subjected to various regimens of sex-steroid hormone replacement have implicated estradiol as one critical determinant of the facilitative effects of repetitive GnRH stimulation on pituitary responsiveness in vivo and in vitro (8)(9)(10)(11)(12)(13)(14)(15)(16). Similarly, short-term administration of estrogen to postmenopausal women is accompanied by altered pituitary responsiveness to exogenously infused GnRH (17,18).…”

Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

“…Consistent with our present finding is the interpretation that estrogen exerts a direct stimulatory action on the pituitary gonadotrophs and thereby increases sensitivity to LRF, and that Clomid may negate this estrogen effect on the pituitary gonadotropin-producing cells, resulting in a reduced LRF responsiveness. Experimental evidence in rats both in vivo and in vitro (17)(18)(19)(20), as well as in humans (9), is rapidly accumulating to support the stimulatory action of a direct estrogen-pituitary feedback. Our recent experiments in humans have afforded a more decisive demonstration in which augmentation of pituitary sensitivity by estrogen can be readily reproduced by the administration in appropriate amounts and duration of estrogen and much smaller doses of LRF in both normal and hypogonadal women (21).…”

Pituitary gonadotropin-releasing hormone receptors. Effects of castration, steroid replacement, and the role of gonadotropin-releasing hormone in modulating receptors in the rat.

“…Clear evidence is available that gonadal steroids modulate gonadotropin responses to GnRH in vivo; castration enhances and androgens inhibit gonadotropin secretion following GnRH administration to male rats (4). Estrogens have a biphasic effect in female rats, initially inhibiting and later enhancing luteinizing hormone (LH) responses to GnRH (5,6). Also, gonadotropin secretion after GnRH varies during both the rat estrous cycle (7)(8)(9)(10)(11) and the menstrual cycle in women (12,13).…”