Skip to main content

Advertisement

SpringerLink
Log in

Epinephrine Biosynthesis: Hormonal and Neural Control During Stress

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

1. Stress contributes to the pathophysiology of many diseases, including psychiatric disorders, immune dysfunction, nicotine addiction and cardiovascular illness. Epinephrine and the glucocorticoids, cortisol and corticosterone, are major stress hormones.

2. Release of epinephrine from the adrenal medulla and glucocorticoids from the adrenal cortex initiate the biological responses permitting the organism to cope with adverse psychological, physiological and environmental stressors. Following its massive release during stress, epinephrine must be restored to replenish cellular pools and sustain release to maintain the heightened awareness and sequelae of responses to re-establish homeostasis and ensure survival.

3. Epinephrine is regulated in part through its biosynthesis catalyzed by the final enzyme in the catecholamine pathway, phenylethanolamine N-methyltransferase (E.C. 2.1.1.28, PNMT). PNMT expression, in turn, is controlled through hormonal and neural stimuli, which exert their effects on gene transcription through protein stability.

4. The pioneering work of Julius Axelrod forged the path to our present understanding of how the stress hormone and neurotransmitter epinephrine, is regulated, in particular via its biosynthesis by PNMT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  • Axelrod, J. (1962). Purification and properties of phenylethanolamine N-methyltransferase. J. Biol. Chem. 237:1657–1660.

    PubMed  CAS  Google Scholar 

  • Axelrod, J., and Reisine, T. D. (1984). Stress hormones: Their interaction and regulation. Science 224:42–49.

    Article  Google Scholar 

  • Berenbeim, D. M., Wong, D. L., Masover, S. J., and Ciaranello, R. D. (1979). Regulation of synthesis and degradation of rat adrenal phenylethanolamine N-methyltransferase. III. Stabilization of PNMT against thermal and tryptic degradation by S-adenosylmethionine. Mol. Pharmacol. 16:482–490.

    PubMed  CAS  Google Scholar 

  • Choi, H. J., Park, S. Y., and Hwang, O. (1999). Differential involvement of PKA and PKC in regulation of catecholamine enzyme genes by PACAP. Peptides 20:817–822.

    Article  PubMed  CAS  Google Scholar 

  • Coupland, R. E., and Tomlinson, A. (1989). The development and maturation of adrenal medullary chromaffin cells of the rat in vivo: A descriptive and quantitative study. Int. J. Dev. Neurosci. 7:419–438.

    Article  PubMed  CAS  Google Scholar 

  • Evinger, M. J., Ernsberger, P., Regunathan, S., Joh, T. H., and Reis, D. J. (1994). A single transmitter regulates gene expression through two separate mechanisms: Cholinergic regulation of phenylethanolamine N-methyltransferase mRNA via nicotinic and muscarinic pathways. J. Neurosci. 14:2106–2116.

    PubMed  CAS  Google Scholar 

  • Evinger, M. J., Towle, A. C., Park, D. H., Lee, P., and Joh, T. H. (1992). Glucocorticoids stimulate transcription of the rat phenylethanolamine N-methyltransferase (PNMT) gene in vivo and in vitro. Cell. Mol. Neurobiol. 12:193–215.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, O., Kim, M. L., and Lee, J. D. (1994). Differential induction of gene expression of catecholamine biosynthetic enzymes and preferential increase in norepinephrine by forskolin. Biochem. Pharmacol. 48:1927–1934.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, O., Park, S. Y., and Kim, K. S. (1997). Protein kinase A coordinately regulates both basal expression and cyclic AMP-mediated induction of three catecholamine-synthesizing enzyme genes. J. Neurochem. 68:2241–2247.

    Article  PubMed  CAS  Google Scholar 

  • Kvetnansky, R., Nemeths, S., Vigas, M., Oprsalova, Z., and Jurcovicova, J. (1984). Plasma catecholamines in rats during adaptation to intermittent exposure to different stressors. In Usdin, E., Kvetnansky, R., and Axelrod, J. (eds.), Stress: The Role of Catecholamines and Other Neurotransmitters. Gordon and Breach Science, New York, pp. 537–562.

    Google Scholar 

  • Morita, K., Bell, R. A., Siddall, B. J., and Wong, D. L. (1996). Neural stimulation of Egr-1 messenger RNA expression in rat adrenal gland: Possible relation to phenylethanolamine N-methyltransferase gene regulation. J. Pharmacol. Exp. Ther. 279:379–385.

    PubMed  CAS  Google Scholar 

  • Morita, K., and Wong, D. L. (1996). Role of Egr-1 in cholinergic stimulation of phenylethanolamine N-methyltransferase promoter. J. Neurochem. 67:1344–1351.

    Article  PubMed  CAS  Google Scholar 

  • Ross, M. E., Evinger, M. J., Hyman, S. E., Carroll, J. M., Mucke, L., Comb, M., Reis, D. J., Joh, T. H., and Goodman, H. M. (1990). Identification of a functional glucocorticoid response element in the phenylethanolamine N-methyltransferase promoter using fusion genes introduced into chromaffin cells in primary culture. J. Neurosci. 10:520–530.

    PubMed  CAS  Google Scholar 

  • Sabban, E. L., and Kvetnansky, R. (2001). Stress-triggered activation of gene expression in catecholaminergic systems: Dynamics of transcriptional events. Trends in Neuroscience 24:91–98.

    Article  CAS  Google Scholar 

  • Stachowiak, M. K., Hong, J. S., and Viveros, O. H. (1990). Coordinate and differential regulation of phenylethanolamine N-methyltransferase, tyrosine hydroxylase and proenkephalin mRNAs by neural and hormonal mechanisms in cultured bovine adrenal medullary cells. Brain Res. 510:277–288.

    Article  PubMed  CAS  Google Scholar 

  • Tai, T. C., Claycomb, R., Her, S., Bloom, A. K., and Wong, D. L. (2002). Glucocorticoid responsiveness of the rat phenylethanolamine N-methyltransferase gene. Mol. Pharmacol. 61:1385–1392.

    Article  PubMed  CAS  Google Scholar 

  • Tai, T. C., and Wong, D. L. (2002). Phenylethanolamine N-methyltransferase gene regulation by cAMP-dependent protein kinase A and protein kinase C signaling pathways. In O’Connor, D. T., and Eiden, L. E. (eds.), The Chromaffin Cell: Transmitter Biosynthesis, Storage, Release, Actions and Informatics. New York Academy of Sciences, New York, pp. 83–95.

    Google Scholar 

  • Tai, T. C., and Wong, D. L. (2003). Protein kinase A and protein kinase C signaling pathway interaction in phenylethanolamine N-methytransferase gene regulation. J. Neurochem. 85:816–829.

    Article  PubMed  CAS  Google Scholar 

  • Thoenen, H., Mueller, R. A., and Axelrod, J. (1970). Neuronally dependent induction of adrenal phenylethanolamine N-methyltransferase by 6-hydroxydopamine. Biochem. Pharmacol. 19:669–673.

    Article  PubMed  CAS  Google Scholar 

  • Tonshoff, C., Hemmick, L., and Evinger, M. J. (1997). Pituitary adenylate cyclase activating polypeptide (PACAP) regulates expression of catecholamine biosynthetic enzyme genes in bovine adrenal chromaffin cells. J. Mol. Neurosci. 9:127–140.

    PubMed  CAS  Google Scholar 

  • Viskupic, E., Kvetnansky, R., Sabban, E. L., Fukuhara, K., Weise, V. K., Kopin, I. J., and Schwartz, J. P. (1994). Increase in rat adrenal phenylethanolamine N-methyltransferase mRNA level caused by immobilization stress depends on intact pituitary-adrenocortical axis. J. Neurochem. 63:808–814.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D. L., Anderson, L. J., and Tai, T. C. (2002a). Cholinergic and peptidergic regulation of phenylethanolamine N-methyltransferase. In O’Connor, D. T., and Eiden, L. E. (eds.), The Chromaffin Cell: Transmitter Biosynthesis, Storage, Release, Actions and Informatics. New York Academy of Sciences, New York, pp. 19–26.

    Google Scholar 

  • Wong, D. L., Bildstein, C. L., Siddall, B., Lesage, A., and Yoo, Y. S. (1993). Neural regulation of phenylethanolamine N-methyltransferase in vivo: Transcriptional and translational changes. Mol. Brain Res. 18:107–114.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D. L., Ebert, S. N., and Morita, K. (1996). Glucocorticoid control of phenylethanolamine N-methyltransferase gene expression: Implications for stress and disorders of the stress axis. In McCarty, R., Aguilera, G., Sabban, E., and Kvetnansky, R. (eds.), Stress: Molecular Genetic and Neurobiological Advances. Gordon and Breach Science, New York, pp. 677–693.

    Google Scholar 

  • Wong, D. L., Ebert, S. N., and Morita, K. (1998a). Neural control of phenylethanolamine-N-methyltransferase via cholinergic activation of Egr-1. In Goldstein, D. S., Eisenhofer, G., and McCarty, R. (eds.), Catecholamines: Bridging Basic Science with Clinical Medicine. Academic Press, San Diego, pp. 77–81.

    Google Scholar 

  • Wong, D. L., Her, S., Tai, T. C., Bell, R. A., Rusnak, M., Farkas, R., Kvetnansky, R., and Shih, J. (2002b). Stress-induced expression of phenylethanolamine N-methyltransferase: Normal and knock out animals. In McCarty, R., Aguilera, G., Sabban, E. L., and Kvetnansky, R. (eds.), Stress: Neural, Endocrine and Molecular Studies. Taylor and Francis, London, pp. 129–135.

    Google Scholar 

  • Wong, D. L., Lesage, A., Siddall, B., and Funder, J. W. (1992). Glucocorticoid regulation of phenylethanolamine N-methyltransferase in vivo. FASEB J. 6:3310–3315.

    PubMed  CAS  Google Scholar 

  • Wong, D. L., Siddall, B., and Wang, W. (1995). Hormonal control of rat adrenal phenylethanolamine N-methyltransferase: Enzyme activity, the final critical pathway. Neuropsychopharmacology 13:223–234.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D. L., Siddall, B. J., Ebert, S. N., Bell, R. A., and Her, S. (1998b). Phenylethanolamine N-methyltransferase gene expression: Synergistic activation by Egr-1, AP-2 and the glucocorticoid receptor. Mol. Brain Res. 61:154–161.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D. L., and Tai, T. C. (2002). Neural mechanisms regulating phenylethanolamine N-methyltransferase gene expression. In Nagatsu, T., Nabeshima, T., McCarty, R., and Goldstein, D. S. (eds.), Catecholamine Research: From Molecular Insights to Clinical Medicine. Kluwer Academic, New York, pp. 135–138.

    Google Scholar 

  • Wong, D. L., Tai, T. C., Wong-Faull, D. C., Claycomb, R., and Kvetnansky, R. (2004). Genetic mechanisms for adrenergic control during stress. In Pacak, K., Aguilera, G., Sabban, E. L., and Kvetnansky, R. (eds.), Stress: Current Neuroendocrine and Genetic Approaches. New York Academy of Sciences, New York, pp. 387–397.

    Google Scholar 

  • Wong, D. L., Zager, E. L., and Ciaranello, R. D. (1982). Effects of hypophysectomy and dexamethasone administration on central and peripheral S-adenosylmethionine levels. J. Neurosci. 2:758–764.

    PubMed  CAS  Google Scholar 

  • Wurtman, R. J., and Axelrod, J. (1965). Adrenaline synthesis: Control by the pituitary gland and adrenal glucocorticoids. Science 150:1464–1465.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA

    Dona Lee Wong

  2. Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, 115 Mill Street, MRC #114, Belmont, Massachusetts, 02478, USA

    Dona Lee Wong

Authors
  1. Dona Lee Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dona Lee Wong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wong, D.L. Epinephrine Biosynthesis: Hormonal and Neural Control During Stress. Cell Mol Neurobiol 26, 889–898 (2006). https://doi.org/10.1007/s10571-006-9056-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-006-9056-6

KEY WORDS:

Search

Navigation