Steroidogenic factor-1: its role in endocrine organ development and differentiation

Abstract

The cloning of the first steroid hormone receptor over a decade ago provided vital insight into the mechanisms by which steroid hormones activate gene transcription. When bound by hormone, these receptors function as ligand-dependent transcription factors by binding to unique response elements in the promoter of specific target genes. Over 60 receptors have now been characterized in this superfamily of steroid receptors. Many receptors known as orphan receptors have been cloned by homology and have no known ligands but appear to be mediators of endocrine function in the adult and in many cases are essential developmental regulators in endocrine organogenesis. One such receptor is steroidogenic factor-1 (SF-1). While initially cloned as a transcriptional regulator of the various steroidogenic enzyme genes in the adrenal and gonad, it has become clear through genetic ablation experiments in mice that SF-1 is an essential factor in adrenal and gonadal development and for the proper functioning of the hypothalamic-pituitary-gonadal axis. In addition, these studies have revealed that SF-1 is necessary for the formation of the ventromedial nucleus of the hypothalamus. While we have learned much since the initial cloning of SF-1, the mechanisms by which SF-1 regulates these various developmental programs remain elusive. This article focuses on the characterization of SF-1 and its emerging role in endocrine homeostasis. Specific attention is placed on the mechanisms of action of this unique member of the nuclear receptor superfamily.