REGULATION BY THYROID-HORMONE AND RETINOIC ACID OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA AND PROTEIN-BETA GENES DURING LIVER DEVELOPMENT

The effect of thyroid hormone and retinoic acid on the expression of C CAAT/enhancer binding proteins (C/EBPs) alpha and beta was investigate d in rat liver during development. Congenital hypothyroidism caused a significant decrease in both C/EBP alpha and C/EBP beta gene expressio n at early stages of postnatal development. This effect was tissue spe cific since thyroid hormone had no effect on the level of C/EBP mRNAs in brown fat. Injection of 15-, and 30-day-old hypothyroid animals wit h thyroid hormone resulted in a slow recovery of the hepatic levels of both C/EBP alpha and beta mRNA levels. Retinoic acid was a very rapid and potent stimulator compared to thyroid hormone in hypothyroid anim als. C/EBP alpha and beta protein levels were markedly diminished in h ypothyroid neonates and the kinetics of induction of these proteins by thyroid hormone was faster than the one observed for the correspondin g transcripts. The discrepancies observed between mRNA and protein lev els suggest a translational or post-translational regulation of these genes as the major point of thyroid hormone action on these genes. (C) 1997 Academic Press.