Interactions of Estradiol and Progesterone on Pituitary Gonadotropin Secretion: Possible Sites and Mechanisms of Action

Abstract

The effects of estradiol (E₂) alone or with progesterone (P) on spontaneous or LHRH-induced releases of LH/FSH were examined 14-19 days after ovariectomy of rats. At 14 days, a Silastic E₂ capsule was implanted s.c. (Day 0) and 72 h later (Day 3) 2 groups of rats received either sesame oil or progesterone (2 mg) s.c. Hourly blood samples were collected sequentially from 1200-1800 h on Day 3 and again at 0900 h and 1600 h on Days 4 and 5 (96 and 120 h post E₂). Control groups included proestrous and untreated ovariectomized rats. Based on the data obtained we concluded that: a) Daily LH but not necessarily FSH surges occur on Days 2, 3, 4 and 5 but not on the day following E₂ treatment (Day 1). b) The responsiveness of the pituitary gland to 250 ng LHRH is equal in both E₂-treated (Day 3) and proestrous rats. However, the magnitude of the spontaneous LH surge in E₂-treated rats (Day 3), was 60% less than in normal proestrous animals. Thus, E₂ seems to reduce the amount of endogenous LHRH released on Day 3. c) Progesterone, given at 0900 h to E₂-treated rats (Day 3), resulted in afternoon LH and FSH surges that were earlier in their onset and of greater magnitude than those in E₂-treated or normal proestrous rats. However, no plasma LH increases occurred in E₂ P-treated rats on Days 4 and 5 unlike in rats receiving only E₂; d) If spontaneous LH surges were blocked with Nembutal on Day 3, the magnitude of the LH surge on Day 4 in E₂-treated rats was 2-fold greater than that observed on Day 4 in rats which spontaneously released LH on Day 3. E₂ P-treated rats which received Nembutal on Day 3 also had spontaneous LH surges on Day 4 which were less in concentration than those of E₂-treated animals on Day 4 or those obtained at 1600 h on Day 3 in the E₂ P-treated group. e) Pituitary gland responsiveness to LHRH in E₂ P-treated rats is equal to that of E₂-treated rats on Day 3. The responsiveness of the pituitary gland on Day 4 in E₂ P-treated rats is significantly less than that in E₂-treated rats on Day 4; however, it is equal to the responsiveness found on Day 3 in E₂ P-treated rats. Therefore, the stimulatory effect of P appears to be due to an increased release of endogenous LHRH. The failure of LH/FSH surges to occur on Day 4 in E₂ P-treated rats may not be due to the loss of 24 h periodicity in the intrinsic neural signal or to a severe decline in the releasable LH pituitary pool. Rather it could be due to the failure of the hypothalamus to discharge sufficient LHRH to evoke LH/FSH surges presumably because of inadequate releasable LHRH reserves.