FSH is produced by the pituitary gonadotrope to regulate gametogenesis. Production of the β-subunit of FSH is the rate-limiting step in FSH synthesis, and a number of peptide and steroid hormones within the reproductive axis have been found to regulate transcription of the FSH β-subunit gene. Although both activin and glucocorticoids are notable regulators of FSHβ by themselves, we find that cotreatment results in a synergistic interaction on the mouse FSHβ promoter at the level of the gonadotrope using transient transfection of a reporter gene into the LβT2 immortalized gonadotrope-derived cell line. This synergistic interaction is specific to FSHβ, because only additive effects of these two hormones are observed on LH β-subunit, GnRH receptor, and mouse mammary tumor virus gene expression. Components of both activin and glucocorticoid signaling are found to be necessary for synergy, and there are specific cis elements on the mouse FSHβ promoter that contribute to the synergistic response as well. We also identify novel activin-responsive regions in the mouse FSHβ promoter and find that the −120 site can bind Smad2/3 in vitro. In addition, the glucocorticoid receptor and Smad3 are sufficient to confer a striking synergy with glucocorticoids on the mouse FSHβ promoter. Our studies provide the first evidence of a synergistic interaction between activin and glucocorticoids within the gonadotrope cell and demonstrate that this synergy can occur directly at the level of the mouse FSHβ promoter.
Thyroid Hormone Inhibition of Human Thyrotropin β-Subunit Gene Expression is Mediated by a Cis-acting Element Located in the First Exon
