Luo X, Ikeda Y, Lala D, Rice D, Wong M, Parker K L
Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):13-8. doi: 10.1016/s0960-0760(98)00146-0.
Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.
类固醇生成因子1（SF-1）是一种孤儿核受体，最初作为细胞色素P450类固醇羟化酶组织特异性表达的关键调节因子被分离出来。此后，对小鼠胚胎发育过程中SF-1表达位点的分析暗示其作用大幅扩展，通过对SF-1基因敲除小鼠的分析显著证实了这些作用。这些SF-1基因敲除小鼠表现出肾上腺和性腺发育不全，伴有内外生殖器从男性向女性的性反转以及因肾上腺皮质功能不全而死亡。这些发现明确表明SF-1对主要类固醇生成器官的胚胎存活至关重要。SF-1基因敲除小鼠的促性腺激素垂体表达也受损，腹内侧下丘脑核（VMH）发育不全，这表明SF-1在丘脑-垂体-性腺轴的所有三个水平调节生殖功能。本文回顾了确定SF-1在内分泌发育中这些重要作用的实验，并强调了未来研究的重要领域。
