THE NUCLEAR RECEPTOR STEROIDOGENIC FACTOR-1 IS ESSENTIAL FOR THE FORMATION OF THE VENTROMEDIAL HYPOTHALAMIC NUCLEUS

The nuclear receptor steroidogenic factor 1 (SF-1) regulates the biosy nthesis of the two essential mediators of male sexual differentiation, androgens and Mullerian-inhibiting substance, and is required for adr enal and gonadal development and gonadotropin expression. SF-1. is als o expressed in the embryonic ventral diencephalon, subsequently locali zing to the ventromedial hypothalamic nucleus, a region important for reproductive behavior. Mice lacking SF-1 secondary to targeted disrupt ion of the Ftz-F1 gene had normal numbers and location of GnRH neurons but exhibited grossly impaired ventromedial hypothalamic nucleus stru cture. Despite their apparently normal GnRH neurons, treatment of Ftz- F1-disrupted mice with GnRH restored pituitary gonadotropin expression , These studies define SF-1's essential role within a discrete hypotha lamic nucleus previously linked to reproduction.