Retinoic acid differentially modulates triiodothyronine and retinoic acid receptors in rat liver according to thyroid status

Abstract

Pallet V, Audouin-Chevallier I, Verret C, Garcin H, Higueret P. Retinoic acid differentially modulates triiodothyronine and retinoic acid receptors in rat liver according to thyroid status. Eur J Endocrinol 1994;131:377–84. ISSN 0804–4643 Triiodothyronine (T3) receptors (TRs) and retinoic acid (RA) receptors (RARs) exert their effects on growth, differentiation and cellular homeostasis by acting as transcription factors. The binding characteristics of these receptors have been studied in liver of hypothyroid and hyperthyroid rats, with or without treatment with T3, RA or T3 + RA together. The changes in binding induced by RA treatment depended on the hormonal status of the rat. In hypothyroid rats the T3 binding capacity was unaltered by administration of T3 or RA alone but increased by 48% after treatment with T3 and RA together. In these rats administration of RA, T3 or T3 + RA increased the RAR binding capacity by 45, 79 and 112%, respectively. In hyperthyroid rats the administration of RA reduced the TR and RAR binding capacities by 22 and 37%, respectively. We found also that the affinity constants of TRs and RARs were reduced in hypothyroid rats after treatment with T3 or T3+RA. It is suggested that this change of the properties of receptors is related to a ligand-dependent conformational change in these receptors. Paul Higueret, Laboratoire de Nutrition, Avenue des Facultés, 33405 Talence Cedex, France