Saulo J A Felizola1, Yasuhiro Nakamura2, Fumitoshi Satoh3, Ryo Morimoto3, Kumi Kikuchi3, Tomohiro Nakamura4, Atsushi Hozawa4, Lin Wang5, Yoshiaki Onodera1, Kazue Ise1, Keely M McNamara1, Sanae Midorikawa6, Shinichi Suzuki7, Hironobu Sasano1. 1. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. 2. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp. 3. Division of Nephrology and Hypertension, Tohoku University Hospital, Sendai, Japan. 4. Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. 5. Department of Physiology, Harbin Medical University Daqing Branch, Daqing, China. 6. Department of Radiation Health Management, Fukushima Medical University, Fukushima, Japan. 7. Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Japan.
Abstract
BACKGROUND: l-glutamate is a major excitatory neurotransmitter in the mammalian brain. Glutamate receptors have been reported in the rat adrenal cortex and in human aldosterone-producing adenomas (APA). However, details regarding the expression levels and functions of these receptors in human adrenocortical tissues remain unknown. METHODS: The mRNA levels of glutamate receptors were evaluated by qPCR in: 12 normal adrenal cortex (NAC), 11 APA, and 12 cortisol-producing adenoma (CPA) tissues. Protein localization was evaluated by immunohistochemistry for 15 NAC, 5 idiopathic hyperaldosteronism cases, 15 APA and 15 CPA. H295R cells were treated with angiotensin-II or forskolin alone or combined with the GRM2/3 agonist LY354740. RESULTS: The level of GRM3 mRNA was higher in APA than in CPA (P=0.0086) or NAC (P=0.0022). GRM1, IGLUR2, and IGLUR3 were also detected in adrenocortical tissues. When added to angiotensin-II/forskolin treatments, LY354740 decreased aldosterone and cortisol production in H295R cells. CONCLUSIONS: GRM3 is considered to regulate steroidogenesis in adrenocortical tissues.
BACKGROUND:l-glutamate is a major excitatory neurotransmitter in the mammalian brain. Glutamate receptors have been reported in the rat adrenal cortex and in humanaldosterone-producing adenomas (APA). However, details regarding the expression levels and functions of these receptors in humanadrenocortical tissues remain unknown. METHODS: The mRNA levels of glutamate receptors were evaluated by qPCR in: 12 normal adrenal cortex (NAC), 11 APA, and 12 cortisol-producing adenoma (CPA) tissues. Protein localization was evaluated by immunohistochemistry for 15 NAC, 5 idiopathic hyperaldosteronism cases, 15 APA and 15 CPA. H295R cells were treated with angiotensin-II or forskolin alone or combined with the GRM2/3 agonist LY354740. RESULTS: The level of GRM3 mRNA was higher in APA than in CPA (P=0.0086) or NAC (P=0.0022). GRM1, IGLUR2, and IGLUR3 were also detected in adrenocortical tissues. When added to angiotensin-II/forskolin treatments, LY354740 decreased aldosterone and cortisol production in H295R cells. CONCLUSIONS:GRM3 is considered to regulate steroidogenesis in adrenocortical tissues.