Epinephrine Biosynthesis: Hormonal and Neural Control During Stress
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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. 22.214.171.124, 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.
KEY WORDS:Epinephrine PNMT stress hormonal regulation neural regulation
- 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.PubMedGoogle 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.PubMedGoogle 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
- 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.PubMedGoogle 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.PubMedCrossRefGoogle 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
- 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.PubMedCrossRefGoogle 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., 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., 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