Coordinate Regulation of the Gonadotropin Subunit Genes in Pituitary and Placenta

Abstract

Each of the glycoprotein hormones is composed of two subunits, the common α-subunit and an individual β-subunit (1). The single α-subunit gene is coordinately expressed with an individual β-subunit gene to form each hormone (2). The chorionic gonadotropin (CG) β-subunit gene is coexpressed with the α-subunit gene in placental trophoblasts, while the thyroid stimulating hormone β-subunit gene is coexpressed with the α-subunit gene in pituitary thyrotropes. In pituitary gonadotropes, both the luteinizing hormone (LH) β-subunit gene and the follicle stimulating hormone (FSH) β-subunit gene are expressed with the α-subunit gene, since both hormones are present in this cell type (3). The mechanism whereby the coordinate transcriptional regulation of the genes encoding these subunits is accomplished is a central issue in understanding the control of glycoprotein hormone regulation. Using molecular methods, including DNA transfections, gel retardation assays, and nuclear protein purification in cell culture model systems, several of the transcriptional regulatory proteins involved in controlling expression of the CG genes in placental trophoblast cells (JEG-3 cell line) and the LH genes in pituitary gonadotrope cells (αT3-1 cell line) have been identified. The nuclear proteins involved in specifying expression include both ubiquitous and cell type-specific transcriptional regulatory proteins. Here we present studies that suggest a mechanism for coordinate control of gonadotropin subunit genes.