Objective:To characterize the unique features of steroidogenic factor-1 (SF-1) among members of the steroid receptor superfamily of proteins and review its role in reproductive development and function.
Methods:We reviewed all pertinent articles that describe structural or functional aspects of SF-1. We also introduced results obtained recently by our group.
Results:Unlike other steroid receptors, SF-1 binds as a monomer to a DNA response element, which is composed of an estrogen receptor “half site.” Furthermore, SF-1 lacks a specific ligand that is required for either interaction with DNA or modulation of its transactivation function. Steroidogenic factor-1 is highly expressed in steroid-producing tissues and in gonadotrophs and plays a pivotal role in regulating the expression of enzymes and hormones essential for steroid biosynthesis pathways. A dramatic phenotype was revealed using SF-1 deficient mice: these mice lack gonads and adrenal glands, establishing SF-1 as an essential embryonic regulator of steroidogenic organ development. While SF-1 is required for basal expression of steroidogenic enzymes, its role in hormone-dependent regulation of reproductive function in vivo is uncertain, but its function may be subject to modulation by coactivators or corespressors and hormones, as well as by post-translational modifications.
Conclusion:Steroidogenic factor-1 plays a key role in the development and differentiation of the reproductive system. Understanding the mechanism of action of SF-1 is expected to provide new clues to the etiology of maldevelopment of the gonads and adrenal glands, and to dysfunctional associated with steroid biosynthesis during early embryonic development and throughout differentiation.
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