Structure-function aspects of the glucocorticoid receptor.

The glucocorticoid receptor belongs to a family of ligand activated nuclear receptors. In addition to steroid hormone receptors, this family also includes receptors for thyroid hormone, retinoic acid and 1,25-dihydroxyvitamin D3 as well as some receptors with as yet unknown ligands, the so called orphan receptors. It is possible that the dioxin receptor is a member of this family as well although this cannot be definitely assessed until the receptor has been cloned. Interestingly, the clofibrate receptor, believed to be involved in clofibrate induction of certain isozymes of cytochrome P-450, has recently been shown to be a member of the steroid receptor supergene family and it is conceivable that other P-450 inducers might act via as yet uncharacterized receptors belonging to the same gene family. Therefore, we should learn significantly about principles of P-450 regulation by considering basic mechanisms of glucocorticoid action; the glucocorticoid receptor probably represents the most extensively studied member of the nuclear receptor family. Our laboratory has been particularly interested in structural aspects of this receptor and has used gene technology to overexpress its different domains, particularly the DNA-binding domain, the structure of which has been resolved using NMR.