title: Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.
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.
authors.affiliation: 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).
authors.forename: Rui
authors.initials: R
authors.lastname: Kishimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoneda
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.forename: Haruya
authors.initials: H
authors.lastname: Ohno
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobuke
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Itcho
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003430:Cross-Sectional Studies; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D011974:Receptors, LH / Q000235:genetics*; D011966:Receptors, LHRH / Q000235:genetics*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484844:GNRHR protein, human; C484274:KCNJ5 protein, human; D012333:RNA, Messenger; D011974:Receptors, LH; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D000450:Aldosterone