STEROID-RECEPTOR ISOFORMS - EXCEPTION OR RULE

Since the first steroid receptor was cloned, it was quickly identified as one of many such receptors constituting a gene superfamily which h as grown to include not only steroid receptors but also receptors for thyroid hormone, retinoic acid, 1,25-dihydroxyvitamin D3 as well as a number of less traditional ligands, including farnesoids and fatty aci ds. Interestingly, these receptors are far outnumbered by the 'orphan' receptors for which ligands are still being sought. The orignal cloni ng of nuclear receptors, although sometimes identifying more than one receptor form, led to the general premise that each ligand has its cog nate receptor through which signal is transduced to the transcriptiona l machinery. Regulation of this process was found to occur at the leve l of receptor expression, ligand availability, and more recently, thro ugh post-translational modifications of the receptor and interaction o f a variety of coactivators/corepressors with the receptor protein. Th e continuing identification of more than a single form for many of the receptors directed the attention of a number of investigators toward defining possible roles for these 'extras'. This review examines the d ifferent forms of nuclear receptor gene family members and how they ma y provide an additional level of regulation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.