Minireview: Steroidogenic Factor 1: Its Roles in Differentiation, Development, and Disease

Mutational screening of NR5A1 gene encoding steroidogenic factor 1 in cryptorchidism and male factor infertility and functional analysis of seven undescribed mutations

“…Mutations in the NR5A1 gene (MIM 184757; encoding steroidogenic factor 1 [SF-1]) have been associated with a spectrum of phenotypes ranging from primary adrenal insufficiency (AI) and complete 46,XY gonadal dysgenesis (6,7), to 46,XX primary AI, 46,XY DSD (disorders of sex development) including hypospadias (8,9), bilateral anorchia (10,11), hypogonadotropic hypogonadism (12), and primary ovarian failure (13)(14)(15)(16). Furthermore, according to the pivotal role of NR5A1 in regulating sex determination and differentiation, testicular descent, and reproduction (6,17), mutations in this gene have been recently associated in preliminary studies with severe forms of male factor infertility (18)(19)(20), with a frequency ranging from 0.7% (19), to 2.2% (20), to 3.5% (18).…”

“…Furthermore, according to the pivotal role of NR5A1 in regulating sex determination and differentiation, testicular descent, and reproduction (6,17), mutations in this gene have been recently associated in preliminary studies with severe forms of male factor infertility (18)(19)(20), with a frequency ranging from 0.7% (19), to 2.2% (20), to 3.5% (18).…”

GnRH pulse frequency differentially regulates steroidogenic factor 1 (SF1), dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1 (DAX1), and serum response factor (SRF): potential mechanism for GnRH pulse frequency regulation of LH beta transcription in the rat

“…DAX1 is a member of the orphan nuclear receptor family, but unlike other members of this family, it lacks the DNA-binding domain and functions via protein-protein interactions [49]. More specifically, DAX1 binds the SF1 C-terminus and interferes with SF1 interaction with other transcriptional coactivators and/or may recruit other corepressors to promoter regions, rather than suppress SF1-DNA binding [24]. Lawson et al [25] reported in LbT2 cells that GnRH at slower pulse frequencies (\1 pulse/hour) significantly increased DAX1 mRNA, but did not affect DAX1 protein expression.…”

“…SF1 is an orphan nuclear receptor with a modular domain structure is composed of an N-terminal zinc finger DNA-binding, a ligand-binding, a C-terminal AF-2 activation domains, and an intervening proline-rich hinge region that has AF-1-like activation activity [24]. It has been reported that GnRH does not stimulate SF1 gene expression in gonadotrope-derived LbT2 cells [19,20,25].…”

The steroidogenic factor-1 protein is not expressed in various forms of endometriosis but is strongly present in ovarian cortical or medullary mesenchymatous cells adjacent to endometriotic foci

“…Several investigators have postulated that in endometriotic stromal cells, prostaglandin E 2 induces aromatase expression at least partially via the transcriptional factor steroidogenic factor-1 (SF-1) (10)(11)(12)(13)(14)(15)(16). SF-1 is one of the key transcription factors that bind and activate the promoters of various steroidogenic genes including steroidogenic acute response protein, side chain cleavage enzyme (P450scc or CYP11A1), 3b-hydroxysteroid dehydrogenase type 2 (HSD3b2), 17-hydroxylase/17-20-lyase (P450c17 or CYP17A1), and aromatase (P450 arom or CYP19A1) (5,11).…”