Effects of Epostane on Ovarian Levels of Progesterone, 17β-Estradiol, Prostaglandin E₂, and Prostaglandin F₂α during Ovulation in the Gonadotropin-Primed Immature Rat*

Abstract

The antiovulatory action of epostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity and progesterone synthesis, was studied in the immature rat. The ovulatory process was induced in 25-day-old rats by injecting them with hCG (10 IU, sc) 2 days after the animals had been primed with PMSG (10 IU). Epostane was administered at different times between 20 h before and 11 h after hCG. Maximum inhibition of ovulation occurred when the drug was given at 3 h after hCG. Epostane inhibited ovulation in a dose-dependent manner when administered in doses ranging from 1.0-50 mg/rat, while exogenous doses of progesterone restored the ovulation rate. A dose of 3.1 mg epostane/rat 3 h after hCG reduced ovarian progesterone levels within 15 min, but the production of this steroid rebounded within 2 h and approached normal levels by 12 h after hCG, i.e. when the follicles began to rupture in control animals. 17 beta-Estradiol synthesis was inhibited just as rapidly, but it remained suppressed for up to 12 h after hCG administration. The ovarian levels of prostaglandins E2 and F2 alpha decreased approximately 30% within 2 h after the administration of epostane, but such a moderate reduction in the synthesis of ovarian prostanoids is usually not sufficient to block ovulation. The results show that epostane has a rapid, but transient, effect on ovarian progesterone synthesis. The temporary decline in the local progesterone level is apparently sufficient to interfere with the normal sequence of metabolic events that lead to the rupture of follicles.

Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation

“…-estradiol synthesis (Espey et al 1990(Espey et al , 1991. Therefore, the present evidence that ovarian PAP-III mRNA is at least partially influenced by ovarian progesterone production is an observation that might not be contradictory to the reported effect of steroids on expression of PAP in the uterus.…”

“…There was minimal expression of PAP-III mRNA at 0 h, but substantial expression at 8 h. In animals treated with the antiovulatory agent indomethacin, which blocks PG synthesis (Espey et al 1991), the signal density was 74·2 14·1%, but this mean was not statistically different from the 8-h control value. In animals treated with the anti-ovulatory agent epostane, which blocks progesterone synthesis (Espey et al 1990), the signal density of 48·2 7·3% was moderately, but significantly (Pc0·05), lower than the 8-h control value. In contrast, the ovaries from a parallel group of gonadotropin-treated animals that were administered (by a procedure described previously (Espey et al 2000a)) 10 mg of exogenous progesterone before the epostane injection exhibited a recovery of the ovarian PAP-III mRNA level to 101·5 10·0% of the 8-h control value (Fig.…”

“…In parallel groups of animals, indomethacin and epostane were injected s.c., also as described previously (Espey et al 2000b). These anti-ovulatory agents were administered at 3 h after hCG in doses of 1·0 mg and 5·0 mg respectively, because these are the intervals after hCG at which these agents are known to block ovarian PG and progesterone effectively (Espey et al 1990, Tanaka et al 1992. The ovarian RNA was extracted from the treated animals at 8 h after hCG, and northern analyses were performed to determine whether blockage of ovarian synthesis of PG or progesterone, or both, affected the transcription of ovarian PAP-III.…”

Evidence that the preovulatory rise in intrafollicular progesterone may not be required for ovulation in cattle

“…It is not known whether the preovulatory increase in the intrafollicular progesterone per se mediates the gonadotropin surge-induced changes in the expression of above regulators of the follicular extracellular matrix in bovine follicles and if such effects are potentially mediated by progesterone-induced regulation of prostanoids, such as prostaglandin (PG)E 2 . Thus, in view of the essential role of progesterone in promoting follicle rupture in other species (Espey et al 1990, Hibbert et al 1996, we hypothesized that the preovulatory increase in the intrafollicular progesterone of the dominant ovulatory follicle is required for ovulation and gonadotropin surge-induced regulation of PGE 2 , PGF 2a , and the above mentioned regulators of extracellular matrix remodeling in bovine preovulatory follicles. Thus, in the present study, intrafollicular injection of a 3b-hydroxysteroid dehydrogenase (3b-HSD) inhibitor (trilostane) to block the preovulatory rise in intrafollicular progesterone was used as a tool to investigate the requirement of increased intrafollicular progesterone for bovine ovulation and gonadotropin surge-induced intrafollicular regulation of mediators of the tissue remodeling process and other molecular, hormonal, and (or) biochemical indices of ovulation and luteinization.…”

Gonadotropin-dependent regulation of bovine pituitary adenylate cyclase-activating polypeptide in ovarian follicles prior to ovulation

“…It has been reported that LH/gonadotropin stimulation selectively induces PR, ADAMTS-1 and progesterone production in granulosa cells of preovulatory follicles; and there is evidence to indicate that progesterone, acting through its nuclear receptor (PR), plays an essential role in the regulation of ovulation (Tsafriri et al 1987, Espey et al 1990). Furthermore, mice deficient for PR not only fail to undergo the expected induction of ADAMTS-1 but also fail to ovulate (Lydon et al 1995, Conneely et al 2000.…”