Specific Induction of Fibronectin Gene in Rat Liver by Thyroid Hormone

Abstract

The regulation of fibronectin (FN) gene expression by thyroid hormone was studied. Rats were rendered hypothyroid by thyroidectomy, and the administration of T4 or T3 was used to produce rats in various thyroid states. RNA was extracted from fresh liver, kidney, and heart, and FN mRNA was determined by dot blot hybridization with a 32P-labeled rat FN cDNA probe. The specificity of the hybridization was assessed by Northern blot analysis. In liver, thyroidectomy decreased the abundance of FN mRNA by half, and daily administration of physiological doses of T4 or T3 for 5-6 days restored FN mRNA to the control level. The administration of pharmacological doses of thyroid hormones induced a further increase in the abundance of FN mRNA. A significant dose-dependent correlation between serum levels of T4 and the abundance of FN mRNA was observed in liver. A receptor-saturating dose of T3 (200 micrograms) given to thyroidectomized rats produced a significant increase in FN mRNA within 6 h after injection, indicating that expression of the FN gene was induced relatively rapidly. Moreover, a nuclear run-off assay revealed that thyroid hormone induces expression of the FN gene at least in part at a transcriptional level. The amount of FN mRNA was also determined in kidney and heart of the same rats. Although the abundance of FN mRNA changed by thyroidectomy or the administration of thyroid hormone in those organs, the magnitude of changes were slight compared with those observed in liver. These results suggested that a marked and dose-dependent induction of the FN gene by thyroid hormone occurs specifically in liver.(ABSTRACT TRUNCATED AT 250 WORDS)