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Journal of Endocrinology (2007) 195, 39-48       DOI: 10.1677/JOE-07-0037
© 2007 Society for Endocrinology
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G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism

Ping Ye, Barbara Mariniello1, Franco Mantero1, Hirotaka Shibata2 and William E Rainey

Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA
1 Department of Medical and Surgery Sciences, University of Padua, Padua 35128, Italy
2 Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan

(Correspondence should be addressed to W E Rainey; Email: wrainey{at}mcg.edu)

The source of aldosterone in 30–40% of patients with primary hyperaldosteronism (PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms causing elevated aldosterone production in APA are unknown. Herein, we examined the expression of G-protein-coupled receptors (GPCRs) in APA and demonstrated that when compared with normal adrenals, there is a general elevation of certain GPCR in many APA and/or ectopic expression of GPCR in others. RNA samples from normal adrenals (n = 5), APAs (n = 10), and cortisol-producing adenomas (CPAs; n = 13) were used on 15 genomic expression arrays, each of which included 223 GPCR transcripts presented in at least 1 out of 15 of the independent microarrays. The array results were confirmed using real-time RT-PCR (qPCR). Four GPCR transcripts exhibited a statistically significant increase that was greater than threefold when compared with normal adrenals, suggesting a general increase in expression when compared with normal adrenal glands. Four GPCR transcripts exhibited a > 15-fold increase of expression in one or more of the APA samples when compared with normal adrenals. qPCR analysis confirmed array data and found the receptors with the highest fold increase in APA expression to be LH receptor, serotonin receptor 4, GnRH receptor, glutamate receptor metabotropic 3, endothelin receptor type B-like protein, and ACTH receptor. There are also sporadic increased expressions of these genes in the CPAs. Together, these findings suggest a potential role of altered GPCR expression in many cases of PA and provide candidate GPCR for further study.




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O Zwermann, Y Suttmann, M Bidlingmaier, F Beuschlein, and M Reincke
Screening for membrane hormone receptor expression in primary aldosteronism
Eur. J. Endocrinol., March 1, 2009; 160(3): 443 - 451.
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