Insulin stimulates thyroid hormone receptor alpha gene expression in cultured bovine aortic endothelial cells.
Thyroid hormones and insulin regulate numerous cell processes and potentially interact through the transcriptional regulation of key genes. For instance, thyroid hormones stimulate the transcription of the fatty acid synthase and malic enzyme genes in chick embryonic hepatocytes, while insulin amplifies these effects. It is possible that insulin augments these actions of thyroid hormone by stimulating production of the thyroid hormone nuclear receptor (TR). In these studies, we examined the regulation of TR production/gene expression by insulin in bovine aortic endothelial cells (BAEC). We demonstrate that insulin significantly stimulates the gene expression of the TR alpha receptor, from BAEC. Insulin causes a maximal threefold induction above control TR alpha steady state mRNA levels in time and dose-related fashion in these cells. The increased mRNA mainly resulted from a twofold increase in transcription, as determined by nuclear run on. Insulin also increases thyroid receptor number and thyroid hormone binding, determined by Scatchard analysis of competitive inhibition binding studies. An established observation is that insulin can synergistically augment thyroid hormone-induced transcriptional activation of several important genes. It has also been previously determined that thyroid hormone action correlates closely to TR nuclear receptor number. Therefore, our studies, which show that insulin stimulates TR alpha production, suggests a potential mechanism whereby insulin can augment thyroid hormone transcriptional action.
Department of Medicine, University of California, Irvine.
R M
RM
Hu
L M
LM
Wu
H J
HJ
Frank
A
A
Pedram
E R
ER
Levin
D000818:Animals; D001011:Aorta; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D014284:Triiodothyronine / Q000378:metabolism
D007328:Insulin; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003907:Dexamethasone