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

Thyroid hormone (triiodothyronine; T 3 ) has been shown to control the expression of β 1 -adrenergic receptors (β 1 -AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T 3 receptors and high expression of the c-erbAα 2 splice variant that interferes with the action of T 3 . To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) α 1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TRα 1 , but not wild-type cells, were responsive to T 3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T 3 exposure. However, T 3 had no effect on β 1 -AR gene expression in either set of cells. The β 1 -AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of β 1 -AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the β 1 -AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of β 1 -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 β 1 -AR gene in C6 cells to T 3 is not due to high expression of c-erbAα 2 but to undefined cell-specific factors.