The Nuclear Hormone Receptor Superfamily: Structure and Function

Members of the nuclear receptor superfamily are ligand-dependent transcription factors that regulate the expression of target genes via binding to specific cis-acting elements (Evans, 1988; Green and Chambon, 1988; Beato, 1989; O’Malley, 1990; Parker, 1990; Wahli and Martinez, 1991; Tsai and O’Malley, 1994). Members of this superfamily respond to endocrine, paracrine, and possibly autocrine signals and therefore modulate diverse aspects of development, differentiation, homeostasis, and behavior in vertebrates. The superfamily consists of receptors for steroid hormones (e.g., estrogens, progestins, androgens, and corticosteroids), steroid derivatives (dihydroxyl vitamin D3), and nonsteroids (retinoids and thyroid hormone). It also includes a growing number of structurally related proteins for which their ligands have yet to be identified, referred to as “orphan receptors,” or members that have lost ligand binding function (e.g., thyroid hormone receptor al and α3; TRα2 and TRα3). In addition, a group of proteins that regulate a variety of developmental pathways in invertebrates, mostly Drosophila melanogaster, also has been classified as members of this superfamily (Table 1) (Amero et al., 1992; Laudet et al., 1992; Parker, 1993; Lutz et al., 1994).