Further Analysis of the Positive Feedback Effects of Estrogen on the Release of Gonadotropin in Women

Abstract

The present experiments were designed to clarify the mechahism of the positive feedback action of estrogen on gonadotropin release. Since a precise hormonal sequence of estrogen and gonadotropin during the induction of gonadotropin surge had been revealed in our previous study (Araki et al., 1978), the same experimental model was used with an additional stimulus of Gn-RH.
The pituitary responsiveness to exogenous Gn-RH during the constant infusion of estradiol-17β was studied in 8 women. The infusion was initiated on various days of the follicular phase and maintained for 66 hr at a constant rate of 500 μg/24 hr which effected final increments of approximately 200-400 pg/ml in circulatory estradiol. Ten or one hundred μg of Gn-RH dissolved in saline was administered i.v. at 3 different times; before estradiol treatment, and 24 hr and 60-64 hr after the onset of the infusion.
In the early f ollicular phase, a markedly decreased responsiveness of the pituitary was observed after the second stimulation of Gn-RH. The suppressive effect of estrogen was not observed in subjects in the mid-follicular phase. The maximal LH response to Gn-RH was seen near or in coincidence with LH surge induced by the stimulus of estradiol.
A prolonged time course during the stimulation of estrogen was divided into 3 different phases: the negative feedback, transition and positive feedback. It is suggested that prolonged exposure to preovulatory levels of estrogen leads to a marked increase in pituitary responsiveness which may elicite LH surge in the absence of a greatly increased release of Gn-RH.