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Medicine (Baltimore). 2016 May;95(20):e3659. doi: 10.1097/MD.0000000000003659.

Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.

Author information

1
From the Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan (RK, KO, MY, HO, KK, KI, NK); and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, Jackson, MS, USA (CEG-S).

Abstract

We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05).We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation.

PMID:
27196470
PMCID:
PMC4902412
DOI:
10.1097/MD.0000000000003659
[Indexed for MEDLINE]
Free PMC Article

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