SF1 in the development of the adrenal gland and gonads

Gokhan Ozisik, John C. Achermann, Joshua J. Meeks, J. Larry Jameson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)94-98
Number of pages5
JournalHormone research
Issue numberSUPPL. 1
StatePublished - 2003


  • Adrenal gland
  • DAX1
  • SF1
  • Sex determination
  • Testis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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