Steroid hormone receptors: activators of gene transcription.

Over the past three decades, a great deal of evidence has accumulated in favor of the hypothesis that steroid hormones act via regulation of gene expression. The action is mediated by specific nuclear receptor proteins, which belong to a superfamily of ligand-modulated transcription factors that regulate homeostasis, reproduction, development and differentiation. This family includes receptors for steroid hormones, thyroid hormones, hormonal forms of vitamin A and D, peroxisomal activators, and ecdysone. Molecular cloning and structure/function analyses have revealed that all members of the steroid/thyroid hormone/retinoic acid receptor family have a similar functional domain structure: a variable N-terminal region, which is involved in modulation of gene expression; a short well-conserved DNA-binding domain, which is crucial for recognition of specific DNA sequences and for receptor dimerization; and a partially conserved C-terminal ligand-binding domain, which is important for hormone binding and also for receptor dimerization and transactivation. In contrast to other members of the receptor superfamily steroid hormone receptors form transient complexes with several heat shock proteins. This interaction promotes proper folding and stability of the receptor molecule. Hormone binding induces a conformational change in the receptor molecule and simultaneously a dissociation of all heat shock proteins, which results in DNA-binding of the hormone-receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)