DOWN-REGULATION OF THYROID-HORMONE RECEPTOR SUBTYPE MESSENGER-RNA LEVELS BY RETINOIC ACID IN CULTURED CARDIOMYOCYTES

The thyroid hormone receptors (TR) and the retinoic acid receptors sha re a high degree of homology and their signaling pathways interplay. T hyroid hormone (T3) is known to be associated with various pathologica l heart conditions. Retinoids are known to ameliorate symptoms in hype rthyroid patients. The aim of this study was to investigate if retinoi c acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated wi th RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours, Solution hybridization for the determination of mRNA for TR al pha(1), alpha(1), beta(1) and beta(2) was performed. RA, T3 and DITPA significantly downregulated the alpha(1), beta(1) and beta(2). The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay . In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease. (C) 1998 Academic Press.