SF1

SF-1, or Steroidogenic Factor 1, is a transcription factor encoded by the NR5A1 gene in humans. It belongs to the nuclear receptor family and is considered an orphan receptor, as no consistent endogenous ligand has been identified. SF-1 serves as a master regulator of steroidogenic tissues, guiding the development and function of the adrenal cortex and gonads and contributing to hormonal regulation in the hypothalamic-pituitary axis.

In embryonic development, SF-1 drives the formation of steroidogenic lineages and activates transcription of several enzymes necessary for steroid biosynthesis, including CYP11A1 and STAR. In the adult, SF-1 maintains steroid hormone production and influences genes involved in reproductive and metabolic processes. SF-1 exerts its effects by binding to specific DNA sequences (SF-1 response elements) as part of the transcriptional machinery and by recruiting coactivators.

Genetic variants in NR5A1 are associated with disorders of sex development and adrenal insufficiency. The observed phenotypes range from gonadal dysgenesis to more subtle gonadal dysfunction, with variable impact on adrenal function. Mouse models lacking Nr5a1 reproduce adrenal and gonadal defects similar to those seen in humans, underscoring the conserved role of SF-1 across species.

Structure-wise, SF-1 contains a DNA-binding domain with zinc finger motifs and a ligand-binding domain typical of nuclear receptors. It generally functions as a transcription factor, capable of acting as a monomer or dimer depending on cellular context.

See also: NR5A1, steroidogenesis.