Hormone response of rodent phenylalanine hydroxylase requires HNF1 and theglucocorticoid receptor

Expression of the rodent phenylalanine hydroxylase (PAH) gene is dependent upon hormones. Induction by glucocorticoids and cAMP occurs slowly and maxi mal stimulation is obtained by a synergistic effect of the two compounds. H ormone responsiveness is conferred by the tissue-specific HSIII enhancer an d involves (i) protein kinase A mediating the cAMP response, even though a consensus sequence for binding of the cAMP response element binding protein is not present; (ii) other serine/threonine kinases as deduced from inhibi tor studies; (iii) glucocorticoid receptor protein bound to glucocorticoid response element half sites; and (iv) binding of the liver-enriched transcr iption factor hepatocyte nuclear factor 1 (HNF1) to sites in the enhancer. Glucocorticoid receptor and HNF1, bound to their cognate sites, cooperative ly increase the glucocorticoid response of the PAH gene, this response bein g synergistically enhanced by cAMP after long-term treatment. (C) 2001 Acad emic Press.