The cell-specific nuclear receptor steroidogenic factor 1 plays multiple roles in reproductive function

Abstract

The cytochrome P450 steroid hydroxylases exhibit tissue-specific and developmentally regulated gene expression. Recent studies showed that the orphan nuclear receptor steroidogenic factor 1 (SF-1) plays a key role in their gene regulation. In mouse embryos, SF-1 expression began at the inception of adrenal and gonadal development, suggesting that SF-1 plays a key role in the steroidogenic cell differentiation. SF-1 was also expressed in the developing pituitary gland and diencephalon, which raised the possibility that it also has additional roles in endocrine development. To examine the role of SF-1 in intact mice, we disrupted the gene encoding SF-1 by homologous recombination in embryonic stem cells; this approach ultimately permitted us to generate SF-1 knockout mice in which the gene encoding SF-1 was inactivated. These studies revealed essential roles of SF-1 in endocrine development that included adrenal and gonadal development, expression of several markers of pituitary gonadotropes, and formation of the ventromedial hypothalamic (VMH) nucleus. These results indicate that SF-1 acts at multiple levels of the reproductive axis to maintain reproductive competence.