Developmental and physiologic roles of the nuclear receptor steroidogenic factor-1 in the reproductive system.

Abstract

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. We reviewed all pertinent articles that describe structural or functional aspects of SF-1. We also introduced results obtained recently by our group. 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 corepressors and hormones, as well as by post-translational modifications. 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 dysfunction associated with steroid biosynthesis during early embryonic development and throughout differentiation.