Glucocorticoid‐Dependent Action of Neural Crest Factor AP‐2: Stimulation of Phenylethanolamine N‐Methyltransferase Gene Expression

: AP‐2 is a vertebrate transcription factor expressed in neural crest cells and their derivative tissues, including the adrenal medulla, where epinephrine is produced. AP‐2 is shown to stimulate expression of the gene encoding the epinephrine biosynthetic enzyme phenylethanolamine N‐methyltransferase (PNMT). However, stimulation of the PNMT gene by AP‐2 requires glucocorticoids and appears to be mediated through the interaction of AP‐2 with activated type II glucocorticoid receptors. Mutation of AP‐2 and/or glucocorticoid receptor binding elements within the PNMT promoter disrupts the ability of AP‐2 and glucocorticoids to induce PNMT promoter activity. These findings suggest, in the case of PNMT, that AP‐2 stimulates gene expression through a novel glucocorticoid‐dependent mechanism.