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Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion: INTRODUCTION(2)

Maintenance of normal reproductive function is dependent on the precise regulation of gonadotropin biosynthesis and secretion. Control of gene expression for the p subunit of both gonadotropins is regulated by circulating gonadal steroids as well as by hypothalamic factors, principally GnRH. In addition to GnRH and gonadal steroids, expression of mRNA for FSHp and secretion of FSH are under the control of the peptide hormones inhibin, activin, and follistatin. The heterodimeric inhibins, designated in-hibin A (apA) and inhibin B (apB) are produced primarily by gonads and act to reduce secretion of FSH. Acti-vins, which are homomeric or heteromeric dimers of the pA and pB chains, are produced in a wide variety of tissues and stimulate synthesis of FSH by direct action on gona-dotropes.

The monomer follistatin probably regulates synthesis and secretion of FSH through its ability to bind activin. Inhibin, activin, and follistatin are produced by the ovary and are present in the circulation, but activin and follistatin are also produced in the pituitary gland by folliculo-stellate cells and by gonadotropes in rats and sheep, and may exert autocrine/paracrine actions on synthesis and secretion of FSH. Like its gonadal homologue, pituitary expression of the follistatin gene varies during the rat estrous cycle and mRNAs for both pB and follistatin increase after gonadectomy in rats. Thus, the local production of activin and follistatin appears to be important in regulating secretion of FSH and represents a potential intrapituitary modifier of hypothalamic or systemic endocrine signals.

The aim of this study was to investigate the possible relationship between the direct effect of estradiol on pituitary gonadotropin secretion and pituitary expression of genes encoding activin (pB) and follistatin. We focused our investigations on the activin pB subunit and follistatin based on previous reports showing that changes in expression of these genes following ovariectomy may be modulated by estradiol. Anestrous ewes were chosen for this study because they are more responsive to estradiol than ewes during the breeding season.