Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein

Abstract

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.