Rm. Hu et al., INSULIN STIMULATES THYROID-HORMONE RECEPTOR-ALPHA GENE-EXPRESSION IN CULTURED BOVINE AORTIC ENDOTHELIAL-CELLS, Molecular and cellular endocrinology, 103(1-2), 1994, pp. 65-71
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.