Developmental Endocrinology Research Group, Clinical & Molecular Genetics Unit, UCL Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
Mol Cell Endocrinol. 2011 Apr 10;336(1-2):198-205. doi: 10.1016/j.mce.2010.11.006. Epub 2010 Nov 13.
Steroidogenic factor-1 (SF-1, Ad4BP, encoded by NR5A1) is a key regulator of adrenal and reproductive development and function. Based upon the features found in Nr5a1 null mice, initial attempts to identify SF-1 changes in humans focused on those rare individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis and Müllerian structures. Although alterations affecting DNA-binding of SF-1 were found in two such cases, disruption of SF-1 is not commonly found in patients with adrenal failure. In contrast, it is emerging that variations in SF-1 can be found in association with a range of human reproductive phenotypes such as 46,XY disorders of sex development (DSD), hypospadias, anorchia, male factor infertility, or primary ovarian insufficiency in women. Overexpression or overactivity of SF-1 is also reported in some adrenal tumors or endometriosis. Therefore, the clinical spectrum of phenotypes associated with variations in SF-1 is expanding and the importance of this nuclear receptor in human endocrine disease is now firmly established.
类固醇生成因子-1（SF-1，Ad4BP，由 NR5A1 编码）是肾上腺和生殖发育和功能的关键调节因子。基于 Nr5a1 缺失小鼠中发现的特征，最初尝试鉴定人类中的 SF-1 变化集中在那些具有原发性肾上腺功能衰竭、46,XY 核型、完全性腺发育不良和 Müllerian 结构的罕见个体上。尽管在两种此类病例中发现了影响 SF-1 DNA 结合的改变，但在肾上腺功能衰竭的患者中并不常见 SF-1 的破坏。相比之下，越来越多的证据表明 SF-1 的变异可与一系列人类生殖表型相关联，例如 46,XY 性发育障碍（DSD）、尿道下裂、无睾症、男性因素不育或女性原发性卵巢功能不全。在一些肾上腺肿瘤或子宫内膜异位症中也报道了 SF-1 的过度表达或过度活性。因此，与 SF-1 变异相关的表型临床谱正在扩大，该核受体在人类内分泌疾病中的重要性现在已得到确立。
