Hyperprolactinemia enhances ovarian estrogen responsiveness to gonadotropins in prepubertal rats: antagonistic effect of adrenalectomy.

Hyperprolactinemia (HP) induced in female rats by dopaminergic receptor blockers enhanced ovarian estradiol (E2) release in response to human chorionic gonadotropin (hCG) or human follicle-stimulating hormone (hFSH) in vitro. Uterine weight and ovarian aromatase activity were also increased. In contrast, ovarian androgen (A) release in response to hCG was reduced. Injections of ovine prolactin (oPrl) also enhanced E2 response to hCG in vitro. The increased E2 response was not due to a direct effect of Prl on ovarian aromatase activity since administration of oPrl to hypophysectomized rats failed to enhance the formation of E2 from testosterone (T) in vitro, and inhibited the increase in the enzyme activity induced by FSH. Adrenalectomy (ADRX) of intact rats, which did not affect mean serum gonadotropin levels, blunted the effect of HP on the E2 response to hCG. The suppression was partially reversed by corticosterone (B). Serum progesterone (P) and T were similar in controls and HP-ovariectomized (OVX) rats with intact adrenals. Likewise, serum androstenedione (delta 4) and dehydroepiandrosterone (DHA) were not altered in intact, HP rats as compared with controls. Thus, an increase in adrenal secretion of these steroids does not appear to mediate the effect of Prl on ovarian E2 response to gonadotropins. Ovaries of HP rats showed more large follicles than controls. In contrast, ovaries of HP-ADRX rats had a decreased number of large follicles. It is suggested that: a) in intact prepubertal rats Prl increases the E2 response of the ovary to gonadotropins by facilitating follicular development rather than by a direct action on aromatase activity, and b) when follicular development is stimulated by FSH, an inhibitory effect of Prl on aromatase activity becomes apparent. The effect of Prl on the E2 response of the ovary to gonadotropins is not mediated by the adrenal cortex. Rather, it appears that while Prl facilitates the development of large, E2-producing follicles by promoting the growth of small- and medium-sized follicles, an adrenal component influences follicular growth at a step subsequent to Prl.