Stress-induced changes in epinephrine expression in the adrenal medulla in vivo

Authors

  • T. C. Tai,

    1. Department of Psychiatry, Harvard Medical School and the Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, Belmont, Massachusetts, USA
    2. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
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    • 1

      The present address of T.C. Tai is the Division of Medical Sciences, Northern Ontario School of Medicine, Laurentian University Campus, Sudbury, ON, Canada.

  • Robert Claycomb,

    1. Department of Psychiatry, Harvard Medical School and the Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, Belmont, Massachusetts, USA
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  • Brenda J. Siddall,

    1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
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  • Rose Ann Bell,

    1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
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  • Richard Kvetnansky,

    1. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic
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  • Dona L. Wong

    1. Department of Psychiatry, Harvard Medical School and the Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, Belmont, Massachusetts, USA
    2. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
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Address correspondence and reprint requests to Dona Lee Wong PhD, Department of Psychiatry, Harvard Medical School, Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, 115 Mill Street, MRC Room 116, Belmont, MA 02478, USA.
E-mail: dona_wong@hms.harvard.edu

Abstract

Immobilization (IMMO) stress was used to examine how stress alters the stress hormone epinephrine (EPI) in the adrenal medulla in vivo. In rats subjected to IMMO for 30 or 120 min, adrenal corticosterone increased to the same extent. In contrast, EPI changed very little, suggesting that EPI synthesis replenishes adrenal pools and sustains circulating levels for the heightened alertness and physiological responses of the ‘flight or fight’ response. In part, stress activates EPI via the phenylethanolamine N-methyltransferase (PNMT) gene as single or repeated IMMO elevated PNMT mRNA. The rise in PNMT mRNA was preceded by induction of the PNMT gene activator, Egr-1, with increases in Egr-1 mRNA, protein, and protein–DNA binding complex apparent. IMMO also evoked changes in Sp1 mRNA, protein, and Sp1–DNA complex formation, although for chronic IMMO changes were not entirely coincident. In contrast, glucocorticoid receptor and AP-2 mRNA, protein, and protein–DNA complex were unaltered. Finally, IMMO stress elevated PNMT protein. However, with seven daily IMMOs for 120 min and delayed killing, protein stimulation did not attain the highly elevated levels expected based on mRNA changes. The latter may perhaps suggest initiation of adrenergic desensitization to prolonged and repeated IMMO stress and/or dissociation of transcriptional and post-transcriptional regulatory mechanisms.

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