SF-1: a key regulator of development and function in the mammalian reproductive system

Abstract

The orphan nuclear receptor steroidogenic factor 1 (SF-1) was isolated as a transcription factor expressed specifically in the mouse primary steroidogenic tissues. SF-1 expression occurs at the earliest stages of adrenal and gonadal development and the expression pattern is sexually dimorphic in gonads during sexual differentiation. The two hormones required for male differentiation, testosterone and Müllerian-inhibiting substance, are regulated by SF-1. Analyses of knockout mice lacking SF-1 by gene targeting disruption demonstrated that the SF-1-disrupted mice lack adrenal glands and gonads, supporting the suggestion that SF-1 is an essential regulator of the endocrine development and differentiation. Additionally, SF-1 is expressed in the pituitary gonadotropes and the ventrolateral hypothalamic nucleus, which are higher levels of the reproductive regulatory axis, of both adults and embryos. These tissues are also affected in SF-1 knockout mice, indicating that SF-1 plays extended roles at all levels of the reproductive axis, by regulating more genes involved in reproductive function and development.