The orphan nuclear receptor steroidogenic factor 1 (SF-1) has emerged as a critical regulator of steroidogenic cell function within the adrenal cortex and gonads. SF-1 also contributes to endocrine development and function at all three levels of the hypotha-lamic-pituitary-gonadal axis. First identified as a regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases, SF-1 subsequently was shown to play considerably broader roles in endocrine function. Knockout mice deficient in SF-1 lacked adrenal glands and gonads and exhibited male-to-female sex reversal of their internal and external genitalia; moreover, they had impaired gonadotrope function and agenesis of the ventromedial hypothalamic nucleus (VMH). These studies delineated multiple essential roles of SF-1 in regulating endocrine differentiation and function. However, the molecular basis underlying these profound consequences of the SF-1 knockout remains to be determined. Moreover, with respect to the biosynthesis of steroids in sites other than the adrenal cortex and gonads, including the neurosteroids, an important goal for further studies is to identify the mechanisms that regulate expression of the steroidogenic enzymes in the absence of SF-1.

From: Contemporary Endocrinology: Neurosteroids: A New Regulatory Function in the Nervous System Edited by: E.-E. Baulieu, P. Robel, and M. Schumacher © Humana Press Inc., Totowa, NJ

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