Androgens, Progestins, and Glucocorticoids Induce Follicle-Stimulating Hormone -Subunit Gene Expression at the Level of the Gonadotrope

FSH is produced by the pituitary gonadotrope to regulate gametogenesis. Steroid hormones, including androgens, progestins, and glucocorticoids, have all been shown to stimulate expression of the FSH subunit in primary pituitary cells and rodent models. Understanding the molecular mechanisms of steroid induction of FSH has been difficult due to the heterogeneity of the anterior pituitary. Immortalized L T2 cells are a model of a mature gonadotrope cell and express the endogenous steroid receptor for each of the three hormones. Transient transfection of each receptor, along with ligand treatment, stimulates the mouse FSH promoter, but induction is severely diminished using receptors that lack the ability to bind DNA, indicating that induction is likely through direct DNA binding. All three steroid hormones act within the first 500 bp of the FSH promoter where six putative hormone response elements exist. The 381 site is critical for FSH induction by all three steroid hormones, whereas the 197 and 139 sites contribute to maximal induction. Interestingly, the 273 and 230 sites are also necessary for androgen and progestin induction of FSH , but not for glucocorticoid induction. Additionally, we find that all three receptors bind the endogenous FSH promoter, in vivo, and specifically bind the 381 site in vitro, suggesting that the binding of the receptors to this element is critical for the induction of FSH by these 3-keto steroid hormones. Our data indicate that androgens, glucocorticoids, and progestins act via their receptors to directly activate FSH gene expression in the pituitary gonadotrope. (Molecular Endocrinology 20: 2062–2079, 2006)