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

Abstract

The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP, encoded by the NR5A1 gene) is an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of cytochrome P450 steroid hydroxylases, studies of both global and tissue-specific knockout mice have demonstrated that SF-1 is required for the development of the adrenal glands, gonads, and ventromedial hypothalamus and for the proper functioning of pituitary gonadotropes. Many genes are transcriptionally regulated by SF-1, and many proteins, in turn, interact with SF-1 and modulate its activity. Whereas mice with heterozygous mutations that disrupt SF-1 function have only subtle abnormalities, humans with heterozygous SF-1 mutations can present with XY sex reversal (i.e. testicular failure), ovarian failure, and occasionally adrenal insufficiency; dysregulation of SF-1 has been linked to diseases such as endometriosis and adrenocortical carcinoma. The current state of knowledge of this important transcription factor will be reviewed with a particular emphasis on the pioneering work on SF-1 by the late Keith Parker.

Intestinal steroidogenesis

“…SF 1 belongs to the superfamily of nuclear receptors, which are mainly ligand depen dent transcription factors. SF 1 binds to the promoter and induces the expression of StAR, CYP 450 steroid hydroxylases, b hydroxy steroid dehydrogenases as well as melanocortine 2 receptor (MC2R), the receptor for ACTH (reviewed in [36]). The phenotype of adrenocortical (and gonadal) insufficiency in SF 1 knockout mice clearly established this transcription factor as pivotal in the development and physiology of steroidogenic tissues [37,38].…”

The Role of Mitochondria in Syncytiotrophoblast Cells: Bioenergetics and Steroidogenesis

“…In gonads or adrenal glands, mutations of the genes encoding for proteins STARD1, CYP11A1 or 3HSD affects steroid production, being SF-1 the main factor regulating P450scc expression (Schimmer & White, 2010). Nevertheless, SF-1 factor is not found in human placenta.…”

Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

“…However, the information about the contribution of DNA methylation in the regulation of steroidogenesis remains unclear. There are a battery of proteins and enzymes that participate in steroidogenesis, such as SF-1, StAR, LDLR, CYP11A1, CYP17A1, and CYP19A1 (Schimmer and White, 2010). The patterns and the extent of DNA methylation particularly in SF-1 gene promoter may be modulated by DNA methylation inhibitor, 5-aza-2¢-deoxycytidine (Azad), and prenatal caffeine ingestion (Liu et al, 2004;Ping et al, 2014).…”