Acute Gonadotropin Release Induced by Exogenous Estradiol During the Mid-Follicular Phase of the Menstrual Cycle

Abstract

During the mid-follicular phase of the cycle (D7-9), a rapid increase in serum estradiol levels was induced via 17P-estradiol infusion, ethinyl estradiol and estradiol benzoate administration in a fashion simulating the preovulatory rise and this elicited an acute release of LH to a lesser degree FSH, in 5 of 7 subjects studied. During treatment (1-3 days) a uniform suppression of gonadotropin levels was noted. This negative feedback effect was followed by the onset of an acute surge of both gonadotropins which occurred 12-24 hrs after the termination of treatment when a consistent drop of serum estradiol concentrations was observed. In three subjects the induced LH-FSH surge was comparable to those occurring spontaneously at midcycle, but without evidence of ovarian response either in ovulation or in the enhanced estradiol secretion.In all subjects, this transient disruption of the normal sequence of gonadotropin secretion was associated with an impairment of follicular maturation as reflected by the low estradiol levels and the prolongation of the follicular phase. The subsequent time course mimicked a newly initiated cycle with an inversed relationship between serum estradiol and gonadotropin concentrations. These data suggest that the negative and positive feedback action of ovarian estradiol modulates the tonic secretion of gonadotropins during the human menstrual cycle and supports the hypothesis that the rapid rise (or acute fall) in serum estradiol levels during the late follicular phase provides a major ovarian signal for triggering the gonadotropin surge at midcycle. (/ Clin Endocr 34: 298, 1972) C OMPELLING evidence that increasing levels of circulating estradiol trigger the ovulatory surge of LH is afforded by the ability of exogenous estradiol to induce acute release of LH in rats (1,2), sheep (3,4), and monkeys (5). Additionally, administration of antibodies to 17|3-estradiol blocks spontaneous and PMS-induced LH surges in rats which can be restored by treatment with a non cross-reacting synthetic estrogen, diethylstilbesterol (6,7). In humans, although ovulation and a rise in plasma LH may be induced by administration of estrogen in

Actions of estradiol on discrete attributes of the luteinizing hormone pulse signal in man. Studies in postmenopausal women treated with pure estradiol.

“…This secondary recovery in LH pulse frequency was associated with a parallel increase in mean and integrated serum LH concentrations. The latter pattern resembles the so-called positive feedback effect of estradiol observed under physiological and various experimental conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). In particular, the present results are consistent with observations in the spontaneously cycling cow, sheep, and human, i.e., estimated LH pulse frequency increases in the late follicular phase as circulating concentrations of estrogenic and other hormones rise before the LH surge (12,33,34).…”

“…7 C). The significantly biphasic responses to estradiol observed here mimic in some respects the classical negative and positive feedback actions ofestradiol that are believed to be exerted during spontaneous normal menstrual cyclicity and occur in postmenopausal individuals in response to other modes of estrogen replacement (1)(2)(3)(4)(5)22). Thus, the present pharmacological model of estrogen action has permitted us to investigate the time-dependent and biphasic impact of estradiol on specific properties of spontaneous pulsatile LH release.…”

“…Investigations ofthe human menstrual cycle suggest that estradiol can exert both negative feedback (suppressive) and positive feedback (facilitative) effects on gonadotropin secretion (1)(2)(3)(4)(5). Moreover, studies in ovariectomized rodents and other mammals subjected to various regimens of sex-steroid hormone replacement have suggested possible actions of estradiol on the hypothalamic release of gonadotropin-releasing hormone (GnRH)' and on the responsiveness of gonadotrope cells to GnRH (6)(7)(8)(9)(10)(11)(12)(13).…”

Importance of Pituitary and Neural Actions of Estradiol in Induction of the Luteinizing Hormone Surge in the Ewe

“…The GnRH signal elicited high-amplitude surges of LH only in the presence of a peak estradiol concentration. Our findings are consistent with the conclusion that two actions are required for a rise in estradiol to elicit a full-amplitude surge of LH in the ewe: an action on the brain to evoke a sudden increase in GnRH release and an action on the pituitary to maximize its response to GnRH.Although it has long been recognized that a rise in circu lating estradiol induces the preovulatory discharge of lu teinizing hormone (LH) in spontaneously ovulating mam mals, the sites and mechanisms through which estradiol acts have been the subject of considerable debate [10,16,17,29,47,51]. On the one hand, increased gonadotropin-releasing hormone (GnRH) secretion during the LH surge has been suggested in the monkey [32,36], rat [43] and sheep [5,6,45], and certainly would seem an important mode of action for estradiol.…”

Clinical Infertility in Women

“…In June 1978 addition to modulating follicular growth and atresia within the ovary, the steroid hormones "feed back" on the hypothalamic-pituitary unit to modulate gonadotrophin synthesis and secretion (9). Thus levels of E2, 17 OH-P, and P in peripheral blood are representative of the concentrations which perfuse the hypothalamic-pituitary unit to modulate gonadotrophin secretion and coordinate interactions of the two components during ovulatory cycles.…”