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

The cloning of the first steroid hormone receptor over a decade ago provide d vital insight into the mechanisms by which steroid hormones activate gene transcription. When bound by hormone, these receptors function as ligand-d ependent transcription factors by binding to unique response elements in th e promoter of specific target genes. Over 60 receptors have now been charac terized in this superfamily of steroid receptors. Many receptors known as o rphan 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 suc h receptor is steroidogenic factor-1 (SF-1). While initially cloned as a tr anscriptional regulator of the various steroidogenic enzyme genes in the ad renal and gonad, it has become clear through genetic ablation experiments i n 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 for mation of the ventromedial nucleus of the hypothalamus. While we have learn ed much since the initial cloning of SF-1, the mechanisms by which SF-1 reg ulates these Various developmental programs remain elusive. This article fo cuses on the characterization of SF-1 and its emerging role in endocrine ho meostasis; Specific attention is placed on the mechanisms of action of this unique member of the nuclear receptor superfamily. (C) 1999 Academic Press .