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

Authors

  • Steven N. Ebert,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Mary Beth Ficklin,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Song Her,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Brenda J. Siddall,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Rose Ann Bell,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Karunesh Ganguly,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Kyoji Morita,

    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author
  • Dona L. Wong

    Corresponding author
    1. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
    Search for more papers by this author

Address correspondence and reprint requests to Dr. D. L. Wong at Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS Building, Room P-106, Stanford, CA 94305-5485, U.S.A.

Abstract

Abstract: 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.

Abbreviations used: DBH, dopamine β-hydroxylase; GC, glucocorticoid; GR, glucocorticoid receptor; GRE, glucocorticoid response element; PNMT, phenylethanolamine N-methyltransferase.

Ancillary