Localization of the Stimulatory Feedback Effect of Estrogen on Ovulation in the Rat

Abstract
The sites of the ovulation-inducing action of estradiol benzoate (EB) and progesterone were studied by intracranial implantation of the crystalline steroids at those times in the rat estrous cycle when systemic administration of the steroids has been shown to advance ovulation (the “Everett effect”). When acute implantation was used, the surgical procedures themselves disrupted the cycle, so a 2-stage operation was adopted with the actual intracranial insertion of the steroid being executed without trauma or anesthesia. Using various experimental paradigms, EB or progesterone implanted in the preoptic, anterior or medial hypothalamic areas did not significantly advance ovulation, by comparison with cholesterol-implanted controls. Implants of estrogen in the pituitary were also ineffective in animals showing 4-day cycles, as also were progesterone implants in that location in 4- or 5-day cyclers. However, intrapituitary implantation of EB on diestrus-2 advanced ovulation by 1 day in 10 of 12 5-day cyclers with a mean ova count of 8.4. None of 7 animals similarly implanted with cholesterol in the pituitary ovulated. Sc progesterone on day 1 converted 4-day cyclers to a 5-day cycle, and ovulation was also advanced in these animals when EB was implanted in the pituitary on diestrus-2. It was concluded that estrogen administered early in the 5-day cycle acts directly on the pituitary gland to precipitate release of gonadotropin, inducing early ovulation. Since the time of vaginal cornification was also significantly advanced by intrapituitary, but not intracerebral, implants, it appears that one consequence of the action of EB on the pituitary is to indirectly increase secretion of endogenous estrogen, the latter probably triggering ovulatory release of gonadotropins. (Endocrinology87: 693,1970)