INSULIN STIMULATES THYROID-HORMONE RECEPTOR-ALPHA GENE-EXPRESSION IN CULTURED BOVINE AORTIC ENDOTHELIAL-CELLS

Thyroid hormones and insulin regulate numerous cell processes and pote ntially interact through the transcriptional regulation of key genes. For instance, thyroid hormones stimulate the transcription of the fatt y acid synthase and malic enzyme genes in chick embryonic hepatocytes, while insulin amplifies these effects. It is possible that insulin au gments these actions of thyroid hormone by stimulating production of t he thyroid hormone nuclear receptor (TR). In these studies, we examine d the regulation of TR production/gene expression by insulin in bovine aortic endothelial cells (BAEC). We demonstrate that insulin signific antly stimulates the gene expression of the TR alpha receptor, from BA EC. Insulin causes a maximal threefold induction above control TR alph a steady state mRNA levels in time and dose-related fashion in these c ells. The increased mRNA mainly resulted from a twofold increase in tr anscription, as determined by nuclear run on. Insulin also increases t hyroid receptor number and thyroid hormone binding, determined by Scat chard analysis of competitive inhibition binding studies. An establish ed observation is that insulin can synergistically augment thyroid hor mone-induced transcriptional activation of several important genes. It has also been previously determined that thyroid hormone action corre lates closely to TR nuclear receptor number. Therefore, our studies, w hich show that insulin stimulates TR alpha production, suggests a pote ntial mechanism whereby insulin can augment thyroid hormone transcript ional action.