Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).
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 (100nM), 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.
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
Yasuhiro
Y
Nakamura
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States; Department of Physiology, Georgia Regents University, Augusta, GA, United States.
Namita G
NG
Hattangady
School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
Ping
P
Ye
Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Fumitoshi
F
Satoh
Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ryo
R
Morimoto
Department of Pathophysiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Takako
T
Ito-Saito
Department of Pathophysiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Akira
A
Sugawara
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Koji
K
Ohba
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kazuhiro
K
Takahashi
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States.
William E
WE
Rainey
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Hironobu
H
Sasano
D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000450:Aldosterone / Q000096:biosynthesis; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011966:Receptors, LHRH / Q000235:genetics* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000450:Aldosterone; D001596:Benzylamines; D002118:Calcium; D019405:Cytochrome P-450 CYP11B2; D007987:Gonadotropin-Releasing Hormone; D007093:Imidazoles; D011966:Receptors, LHRH; D013449:Sulfonamides; C484844:GNRHR protein, human; C072105:KN 93; D000096926:Benzenesulfonamides; C031938:calmidazolium
Adrenal aldosterone-producing adenoma (APA); Aldosterone; CYP11B2; Gonadotropin-releasing hormone receptor (GnRHR)