title: Steroidogenic factor-1 and human disease.
abstract: Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene encoding Sf-1 (Nr5a1) in mice results in severe developmental defects of the adrenal gland and gonad. Consequently, initial work on the potential effects of SF-1 disruption in humans focused on individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis, and Müllerian structures. This is a rare phenotype, but has been reported on two occasions, because of alterations that affect key DNA-binding domains of SF-1. Attention then turned to a potential wider role of SF-1 in human adrenal and reproductive disorders. Although changes in SF-1 only very rarely cause isolated adrenal failure, it is emerging that variations in SF-1 are a surprisingly frequent cause of reproductive dysfunction in humans. In 46,XY disorders of sex development, a spectrum of phenotypes has been reported including severe and partial forms of gonadal (testicular) dysgenesis, hypospadias, anorchia with microphallus, and even male factor infertility. In 46,XX females, alterations in SF-1 are associated with primary ovarian insufficiency. Thus, SF-1 seems be a more significant factor in human reproductive health than was first envisioned, with implications for adults as well as children.
authors.affiliation: Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Ranna
authors.initials: R
authors.lastname: El-Khairi
authors.forename: John C
authors.initials: JC
authors.lastname: Achermann
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000309:Adrenal Insufficiency / Q000209:etiology; D000818:Animals; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012734:Disorders of Sex Development / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1