NUCLEAR receptors mediate the signals of a broad variety of fat-soluble hormones, including the steroid and vitamin D₃ hormones, thyroid hormones, and vitamin A-derived hormones and analogs (retinoids). The receptors represent one of the largest transcription factor families known (reviewed in Refs. 1–3). Only some of the members are ligand-binding receptors, while others are “orphan receptors” for which specific ligands have not yet been identified and may not exist. These proteins may therefore function as constitutive or negative transcription factors, or coregulators of ligand-binding receptors. The receptors regulate gene transcription by interacting with specific DNA sequences (called response elements) that are usually located in the promoter regions of the responsive genes.

All receptors contain a highly conserved cysteine-rich region, the DNA- binding domain (DBD) that forms two “zinc-finger” structures that allow protein-DNA as well as proteinprotein interaction (4). A second but less well conserved region is found in all receptors in the hydrophobic carboxyterminal half and is usually referred to as the ligand-binding domain (LBD). In addition to ligand recognition, this domain encodes receptor dimerization (5–7) and transactivation (6, 8), or repressor functions (6, 9).