Steroidogenic factor 1 (SF-1) is essential for endocrine development and function

Steroidogenic factor 1 (SF-I), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-I expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-I knockout mice. These SF-I knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogrenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary-gonadal axis. This article reviews the experiments that have defined these essential roles of SF-I in endocrine development and highlights important areas for future studies. (C) 1999 Elsevier Science Ltd. All rights reserved.