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Horm Metab Res 2011; 43(2): 106-111
DOI: 10.1055/s-0030-1269899
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© Georg Thieme Verlag KG Stuttgart · New York

Aldosterone Producing Adrenal Adenomas are Characterized by Activation of Calcium/Calmodulin-dependent Protein Kinase (CaMK) Dependent Pathways

S. Sackmann1 , U. Lichtenauer2 , I. Shapiro2 , M. Reincke2 , F. Beuschlein2
  • 1Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany
  • 2Medical Clinic, University Hospital Innenstadt, Ludwig Maximilians University, Munich, Germany
Further Information

Publication History

received 21.08.2010

accepted 22.11.2010

Publication Date:
19 January 2011 (online)

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Abstract

Primary aldosteronism is the most prevalent cause of secondary hypertension. However, insights in pathophysiological mechanisms resulting in autonomous aldosterone secretion are limited. Although transcriptional regulators of aldosterone synthase (CYP11B2) including calcium-binding calmodulin kinase (CaMK) dependent pathways have been defined in vitro, it remains uncertain whether these mechanisms play a role in the context of dysregulated steroidogenesis in aldosterone producing adrenadenomas. Thus, we compared expression and activation of key components of CaMK pathways in aldosterone producing adenomas (APAs) with normal adrenals glands (NAGs). As expected, aldosterone synthase expression in APAs was significantly higher in comparison to NAGs, suggesting transcriptional activation as a contributing factor of aldosterone excess. Along the same line, CaMKI was significantly upregulated in APAs on the mRNA and protein level. Furthermore, immunohistochemistry revealed nuclear localization of CaMKI in these tumors. The phosphorylation of CREB, a target protein for CaMKI was increased, which could represent a further stimulation of aldosterone synthase transcription. In summary, this study provides indirect evidence for a causative involvement of the CaM kinase signaling pathway in human aldosterone producing adenomas.

Key words

CaMKI - autonomous aldosterone secretion - CaM kinase dependent pathways - primary aldosteronism

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Correspondence

F. BeuschleinMD 

Division of Endocrine Research

Department of Medicine

Innenstadt

University Hospital Munich

Ziemssenstraße 1

80336 Munich

Germany

Phone: +49/89/5160 2110

Fax: +49/89/5160 4467

Email: felix.beuschlein@med.uni-muenchen.de

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