Activin modulates differential effects of estradiol on synthesis and secretion of follicle-stimulating hormone in ovine pituitary cells

In several physiological paradigms, secretion of FSH and LH are not coordin ately regulated, Because these hormones appear to be produced by a single c ell type in the anterior pituitary gland, their discordant regulation must be related to differential intracellular responses to various stimuli. Estr adiol-17 beta (estradiol) has been shown to influence secretion of both FSH and LH and some of its effects are mediated directly on the gonadotrope, C hanges in expression of intrapituitary factors such as activin and follista tin may mediate effects of estradiol and account for discordant patterns of FSH and LH. The aims of this study were 1) to determine if estradiol alter s expression of genes encoding activin, follistatin, or both in ovine pitui tary cells; and 2) to observe the effects of immunoneutralizing activin B i n vitro on gonadotropin secretion. Pituitary cells from five ewes in the an estrous season were cultured for 24 h with estradiol (0.01 or 1.0 nM). Estr adiol reduced basal secretion of FSH in a dose-dependent manner (P < 0.001) and simultaneously increased basal secretion of LH (P < 0.001), Decreased secretion of FSH in estradiol-treated cultures was accompanied by suppresse d levels of FSH beta subunit mRNA (P < 0.001). Amounts of mRNA for activin <beta>(B) were reduced in a dose-dependent manner by estradiol (27% +/- 4.9 % at 0.01 nM, P < 0.02; and 46% <plus/minus> 3.9% at 1.0 nM, P < 0.002). In contrast, mRNA for follistatin was not affected by treatment with estradio l, Treatment of pituitary cells with an antibody to activin B reduced secre tion of FSH by 50% (P < 0.01) without influencing secretion of LH. These da ta lead us to conclude that discordant secretion of gonadotropins can be in duced by estradiol acting directly at the pituitary level. The inhibitory e ffect of estradiol on FSH secretion may be mediated indirectly through decr eased pituitary expression of the activin gene.