Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA)

Yasuhiro Nakamura, Namita G. Hattangady, Ping Ye, Fumitoshi Satoh, Ryo Morimoto, Takako Ito-Saito, Akira Sugawara, Koji Ohba, Kazuhiro Takahashi, William E. Rainey, Hironobu Sasano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100. nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume384
Issue number1-2
DOIs
Publication statusPublished - 2014 Mar 25

Keywords

  • Adrenal aldosterone-producing adenoma (APA)
  • Aldosterone
  • CYP11B2
  • Gonadotropin-releasing hormone receptor (GnRHR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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