Mechanism of Stimulatory Feedback Effect of Estradiol Benzoate on the Pituitary

Abstract

Experiments were conducted to investigate the mechanism whereby intrapituitary implantation of crystalline estradiol benzoate (EB) on diestrus-2 advances ovulation by 1 day in rats showing 5-day estrous cycles; or 4- day rats converted to a 5-day cycle by progesterone on metestrus (diestrus-1). Sodium pentobarbital early in the afternoon of the day following implantation prevented advancement of ovulation. It was restored in 50% of animals after administration of a submaximal dose of an ovine gonadotropin releasing factor preparation. To determine the required period of action of estrogen on the pituitary, implants were allowed to remain in situ for different periods of time at different stages of the cycle. Twenty-four hr implantation from the morning of diestrus-2 was effective, in contrast to similar implantation 1 day later. When implants were placed for shorter periods of time on diestrus-2, it was found that implantation from 1 to 5 PM advanced ovulation in all of 9 rats tested. This period of exposure was more effective than was 9 AM to 1 PM or 5 PM to 9 PM. The effect of the 4 hr afternoon exposure to estrogen was blocked by administration of pentobarbital just before implantation. Evidence that the implant precipitates early endogenous estrogen secretion was as follows: 1) Vaginal cornification was also advanced by 1 day in animals with advanced ovulation. 2) The appearance of mating behavior (lordosis) also occurred 1 day early following intrapituitary but not intracerebral EB implantation. It was concluded that estrogen acts on the pituitary early in the 5-day cycle to decrease the threshold to the hypothalamic gonadotropin releasing influence, resulting in a 4- day cycle in the experimental and presumably also the natural situation. The initial brief exposure to EB apparently triggers a chain of events which includes an early rise in endogenous production of estrogen. (Endocrinology88: 293, 1971)