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Cited by 53Stress Responses and CortisolNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

Gene expression of phenylethanolamine N-methyltransferase in corticotropin-releasing hormone knockout mice during stress exposure

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Kvetnansky, R., Kubovcakova, L., Tillinger, A., Micutkova, L., Krizanova, O., Sabban, E. L.·2006·Cellular and Molecular Neurobiology
DOI 10.1007/s10571-006-9063-7PMC PMC11520757
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Abstract

Aims Epinephrine (EPI) synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) is primarily localized in the adrenal medulla (AM). We have recently described existence of the PNMT gene expression in cardiac atria and ventricles and in sympathetic ganglia of adult rats and mice. The aim of the present work was to study regulation of the PNMT gene expression in corticotropin-releasing hormone knockout mice (CRH KO) and matched control wild-type mice (WT) under normal and stress conditions.Methods Levels of the PNMT mRNA were determined by RT-PCR; PNMT immunoprotein and protein of transcription factor EGR-1 by Western Blot. Plasma EPI and corticosterone (CORT) levels were determined by radioenzymatic and RIA methods. Immobilization (IMMO) was used as a stressor.Results Stress-induced increases in the PNMT mRNA and protein levels observed in WT mice were almost completely absent in CRH KO mouse adrenal medulla, stellate ganglia, and cardiac atria, while ventricular PNMT mRNA elevation was not CRH-dependent. Plasma EPI and CORT levels were markedly reduced in CRH KO compared to WT mice both before and after the stress. Levels of EGR-1, crucial transcription factor for regulation of the PNMT were highly increased in stressed WT and CRH KO mice in cardiac areas, but not in the adrenal medulla.Conclusions Data show that the CRH deficiency can markedly prevent immobilization-triggered induction of the PNMT mRNA and protein levels in the adrenal medulla and stellate ganglia. Reduced plasma epinephrine and corticosterone levels and adrenal medullary EGR-1 protein levels in CRH knockout versus WT mice during stress indicate that the HPA axis plays a crucial role in regulation of the PNMT gene expression in these organs. Cardiac atrial PNMT gene expression with stress is also dependent on intact HPA axis. However, in cardiac ventricles, especially after the single stress exposure, its expression is not impaired by CRH deficiency. Since cardiac EGR-1 protein levels in CRH KO mice are also not affected by the single stress exposure, we propose existence of different regulation of the PNMT gene expression, especially in the cardiac ventricles.Overall, our findings reveal that the PNMT gene expression is regulated through the HPA in both sympathoadrenal system and the heart and also via EGR-1 in the adrenal medulla, but apparently not in the heart. Regulation of the PNMT gene expression in various compartments of heart includes both corticosterone-dependent and independent mechanisms.

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Research works printed but not linked: 5

  1. Axelrod, J. (1957). O-methylation of catechol amines in vitro and in vivo. Science126:400–401. [DOI] [PubMed] [Google Scholar]
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Authors
Kvetnansky, R., Kubovcakova, L., Tillinger, A., Micutkova, L., Krizanova, O., & Sabban, E. L.
Affiliations
  • Slovak Academy of Sciences (SK)
  • New York Medical College (US)
ORCID
Venue
Cellular and Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2006-05-12
Volume
26
Issue
4-6
Pages
733-752
ISSN
  • 0272-4340 (ISSN-L)
  • 1573-6830
DOI
10.1007/s10571-006-9063-7
PMC
PMC11520757
OpenAlex
W2062111719
Cited by
53
References
76
Citations by year
2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 7 · 2012: 5
FWCI
10.34
Type
book chapter
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Neurobiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Slovenská Akadémia Vied
  • Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
  • National Institute of Neurological Disorders and Stroke (R01NS044218, NS44218)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
phenylethanolamine N-methyltransferase, epinephrine synthesis, hypothalamic-pituitary-adrenal axis, restraint stress, EGR1, adrenal medulla, atrium, cardiac ventricle, stellate ganglion, corticosterone, stress response, gene expression regulation, sympathoadrenal system, heart-brain interaction
MeSH terms
Adrenal Medulla, Animals, Corticotropin-Releasing Hormone, Epinephrine, Gene Expression Regulation, Heart Atria, Heart Ventricles, Immobilization, Male, Phenylethanolamine N-Methyltransferase, Stellate Ganglion, Stress, Physiological, Gene Expression, Mice, Knockout, Mice, Early Growth Response Protein 1

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