Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: the metabotropic pathway.
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.
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Saulo J A
SJA
Felizola
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
Yasuhiro
Y
Nakamura
Division of Nephrology and Hypertension, Tohoku University Hospital, Sendai, Japan.
Fumitoshi
F
Satoh
Division of Nephrology and Hypertension, Tohoku University Hospital, Sendai, Japan.
Ryo
R
Morimoto
Division of Nephrology and Hypertension, Tohoku University Hospital, Sendai, Japan.
Kumi
K
Kikuchi
Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Tomohiro
T
Nakamura
Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Atsushi
A
Hozawa
Department of Physiology, Harbin Medical University Daqing Branch, Daqing, China.
Lin
L
Wang
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Yoshiaki
Y
Onodera
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kazue
K
Ise
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Keely M
KM
McNamara
Department of Radiation Health Management, Fukushima Medical University, Fukushima, Japan.
Sanae
S
Midorikawa
Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Japan.
Shinichi
S
Suzuki
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Hironobu
H
Sasano
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013997:Time Factors
D001643:Bridged Bicyclo Compounds; D018094:Receptors, Metabotropic Glutamate; D013256:Steroids; D000450:Aldosterone; D000242:Cyclic AMP; D013252:Steroid 11-beta-Hydroxylase; C104753:eglumetad; D006854:Hydrocortisone
APA; Adrenal cortex; Adrenocortical adenoma; Aldosterone; CPA; Glutamate receptor; NAC; ZF; ZG; ZR; Zona glomerulosa; aldosterone producing adenoma; cAMP; cortisol producing adenoma; normal adrenal cortex; qPCR; quantitative RT-PCR; zona fasciculata; zona glomerulosa; zona reticularis