POSTTRANSCRIPTIONAL INDUCTION OF BETA(1)-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 beta(1)-adrenergic receptors (beta(1)-AR) in cardiac myo cytes, but not in C6 glioma cells. This cell specificity has been attr ibuted to low expression of T-3 receptors and high expression of the c -erbA alpha(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) alpha(1) gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TR alpha(1), but not wil d-type cells, were responsive to T-3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T-3 exposur e. However, T-3 had no effect on beta(1)-AR gene expression in either set of cells. The beta(1)-AR mRNA concentrations were, however, altere d by retinoic acid (RA) treatment, Retinoic acid caused a rapid up-reg ulation of beta(1)-AR mRNA levels that was blocked by cycloheximide. R etinoic acid did not increase the beta(1)-AR gene transcription rate i n run-on experiments. These results indicate an indirect post-transcri ptional effect of RA. Control of beta(1)-AR expression in C6 cells is also exerted at the translational level, because there was no correlat ion between mRNA and protein induction, as determined by radioligand b inding studies. We conclude that lack of responsiveness of the beta(1) -AR gene in C6 cells to T-3 is not due to high expression of c-erbA al pha(2) but to undefined cell-specific factors.