SF1 in the Development of the Adrenal Gland and Gonads
- 1 January 2003
- journal article
- review article
- Published by S. Karger AG in Hormone Research in Paediatrics
- Vol. 59 (Suppl. 1), 94-98
- https://doi.org/10.1159/000067831
Abstract
SF1 (steroidogenic factor-1; NR5A1) is an orphan nuclear receptor that is expressed in the adrenal gland, gonads, spleen, ventromedial hypothalamus and pituitary gonadotroph cells. Combined approaches of targeted mutagenesis in mice and examination of the effects of naturally occurring mutations in humans have clarified the role of SF1 in steroidogenesis and development. Targeted disruption of Sf1 (Ftzf1) in mice prevents gonadal and adrenal development and causes male-to-female sex reversal. A heterozygous loss-of-function human SF1 mutation (G35E) was described in a patient with adrenal failure and complete 46,XY sex reversal, indicating that haploinsufficiency of this transcription factor is sufficient to cause a severe clinical phenotype. In an infant with a similar clinical phenotype, a homozygous SF1 mutation (R92Q) was identified. In functional assays, this mutant SF1 protein exhibited partial loss of DNA binding and transcriptional activity when compared with the more severe G35E P-box mutant. These patients reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans.Keywords
This publication has 18 references indexed in Scilit:
- Gonadal Determination and Adrenal Development Are Regulated by the Orphan Nuclear Receptor Steroidogenic Factor-1, in a Dose-Dependent MannerJournal of Clinical Endocrinology & Metabolism, 2002
- Comparative localization of Dax‐1 and Ad4BP/SF‐1 during development of the hypothalamic‐pituitary‐gonadal axis suggests their closely related and distinct functionsDevelopmental Dynamics, 2001
- Apparently Normal Ovarian Differentiation in a Prepubertal Girl with Transcriptionally Inactive Steroidogenic Factor 1 (NR5A1/SF-1) and Adrenocortical InsufficiencyAmerican Journal of Human Genetics, 2000
- A Naturally Occurring Steroidogenic Factor-1 Mutation Exhibits Differential Binding and Activation of Target GenesPublished by Elsevier BV ,2000
- Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine developmentMolecular Endocrinology, 1996
- The Mouse Ftzf1 Gene Required for Gonadal and Adrenal Development Maps to Mouse Chromosome 2Genomics, 1995
- The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleusMolecular Endocrinology, 1995
- A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiationCell, 1994
- Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiationNature, 1994
- Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive elementNature, 1989