Development Of Fetal Bovine Ovaries: Regulation Of Steroid Production, Role Of Endogenous Steroids, And Mechanisms Of Steroid Action

Abstract

In bovine ovaries, a pool of primordial follicles forms before birth. Progesterone and estradiol can inhibit formation and activation of primordial follicles in fetal ovarian tissue in vitro. Fetal ovarian capacity to produce steroids decreases around the time follicles form. The roles, regulation, and mechanisms of action of progesterone and estradiol in early ovarian development remain unclear. Three hypotheses were tested: 1) LH and FSH can stimulate fetal ovarian steroid production, 2) endogenous progesterone and estradiol can inhibit follicle formation and activation and 3) nuclear steroid receptors mediate the inhibitory effects of progesterone and estradiol. To test these hypotheses, pieces of fetal bovine ovaries were cultured under various conditions and the accumulation of progesterone and estradiol in the medium and/or numbers of follicles in ovarian pieces were determined. LH and FSH had dose-dependent, differential effects on ovarian steroid production; LH increased androgen production and FSH stimulated aromatization of testosterone (T) to estradiol. These results suggest the presence of two different cell types in the fetal ovary, one that responds to LH by producing androgens and another that responds to FSH by converting androgens to estrogens. Treatment with LH+FSH, T, and T+FSH increased the accumulation of total steroid (progesterone + estradiol) in the culture medium. LH+FSH and T+FSH inhibited follicle formation and activation whereas there was only a tendency for T to inhibit follicle development. Reduction of estradiol production in cultures with T+FSH with an aromatase inhibitor partially reversed the inhibition of follicle development by T+FSH. Antagonists for the progesterone receptor (RU 486) or estrogen receptors (ICI 182,780) completely reversed the inhibition of follicle formation by exogenous progesterone and estradiol, respectively. Furthermore, use of agonists or antagonists specific for estrogen receptor [alpha] or estrogen receptor [beta] showed that both receptors can mediate the inhibition of follicle development by estradiol. Taken together, the results support the initial hypotheses. Furthermore, they suggest that steroidogenesis is regulated similarly in adult and fetal ovaries, that fetal ovarian progesterone and estradiol are negative regulators of follicle formation and activation in vivo, and that inhibitory effects of steroids can be mediated through their nuclear receptors.