Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors.
Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of beta 1-adrenergic receptors (beta 1-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-erbA alpha 2 splice variant that interferes with the action of T3. 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 wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of beta 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 beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors.
López-Barahona
M
M
Departamento de Investigación, Pharmacia-Antibióticos, SA, Madrid, Spain.
Iglesias
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T
García-Higuera
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I
Mayor
F
F
Zaballos
A
A
Bernal
J
J
Muñoz
A
A
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D003720:Densitometry; D004082:Dihydroalprenolol / Q000032:analysis / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D018776:Genes, erbA / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011869:Radioligand Assay; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D014316:Tritium; D014212:Tretinoin; D004082:Dihydroalprenolol