Post-transcriptional induction of β1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors

Abstract

Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of β1-adrenergic receptors (β1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbAα2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) α1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TRα1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on β1-AR gene expression in either set of cells. The β1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of β1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the β1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of β1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the β1-AR gene in C6 cells to T3 is not due to high expression of c-erbAα2 but to undefined cell-specific factors.