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

Steroidogenic factor 1 (SF-I), an orphan nuclear receptor, initially was is olated as a key regulator of the tissue-specific expression of the cytochro me P450 steroid hydroxylases. Thereafter, analyses of sites of SF-I express ion during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses o f SF-I knockout mice. These SF-I knockout mice exhibited adrenal and gonada l agenesis, associated with male-to-female sex reversal of their internal a nd external genitalia and death from adrenocortical insufficiency. These fi ndings showed unequivocally that SF-1 is essential for the embryonic surviv al of the primary steroidogrenic organs. SF-1 knockout mice also had impair ed pituitary expression of gonadotropins and agenesis of the ventromedial h ypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive fu nction 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 st udies. (C) 1999 Elsevier Science Ltd. All rights reserved.