Thyroid hormone and retinoic acid receptors - ligand inducible transcription factors: up- or down-regulation of nuclear receptor expression in vivo

Regulation of gene expression by both thyroid hormones arid vitamin A-deriv ed "retinoid hormones" is a critical component in controlling many aspects of higher vertebrate development and metabolism. The functions of retinoids and thyroid hormones are mediated by nuclear receptors, which comprise a l arge superfamily of ligand-inducible transcription factors. Four major func tional domains have been identified in all members of the receptor super fa mily. The carboxy-terminal domain is responsible for hormone binding and di merization of nuclear receptors, and it is critical in transcriptional acti vation and repression. The ligand-nuclear receptor complexes regulate gene expression through binding to short cia-acting DNA sequences - hormone resp onsive elements. Both thyroid hormone receptors (TR) and all-trans retinoic acid receptors (RAR) are capable to function as transcriptional repressors in the absence of specific ligands and potent activators upon binding thyr oid hormone or all-trans retinoic acid. 9-cis retinoic acid receptors (RXR) play a central role in tie regulation of many intracellular signalling pat hways and can mediate ligand-dependent transcription as well. In this study data are presented on a possible modulation of either the TR or the RAR co ncentration and/or expression in the rat liver or spleen in different exper imental models (partial hepatectomy, laparotomy, adjuvant arthritis, immobi lization stress or 2-deoxy-D-glucose-induced intracellular glucopenia).