Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: The metabotropic pathway

• Published in: Molecular and cellular endocrinology Vol. 382; no. 1; pp. 170 - 177
• Main Authors: Felizola, Saulo J.A., Nakamura, Yasuhiro, Satoh, Fumitoshi, Morimoto, Ryo, Kikuchi, Kumi, Nakamura, Tomohiro, Hozawa, Atsushi, Wang, Lin, Onodera, Yoshiaki, Ise, Kazue, McNamara, Keely M., Midorikawa, Sanae, Suzuki, Shinichi, Sasano, Hironobu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25.01.2014
• Subjects: Adrenal cortex; Adrenal Glands - drug effects; Adrenal Glands - metabolism; Adrenocortical adenoma; Aldosterone; Aldosterone - metabolism; Animals; Blotting, Western; Brain; Bridged Bicyclo Compounds - pharmacology; cAMP; Cell Line, Tumor; Control; Cortexes; Cyclic AMP - metabolism; Endocrinology; Glutamate receptor; Glutamates; Human; Humans; Hydrocortisone - metabolism; Immunohistochemistry; Neurotransmitters; Polymerase Chain Reaction; Rats; Receptors; Receptors, Metabotropic Glutamate - metabolism; Signal Transduction - drug effects; Steroid 11-beta-Hydroxylase - metabolism; Steroids - biosynthesis; Time Factors; Zona glomerulosa; Zona glomerulosa; Adrenal cortex; Glutamate receptor; ZF; Adrenocortical adenoma; cAMP; Aldosterone; ZG; NAC; APA; CPA; ZR; qPCR; cortisol producing adenoma; zona fasciculata; aldosterone producing adenoma; quantitative RT-PCR; zona reticularis; normal adrenal cortex
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2013.09.025

•Glutamate receptors GRM1, GRM3, IGLUR2, and IGLUR3 were detected in human adrenocortical tissues.•GRM3 was significantly higher in aldosterone producing adenomas than in the normal adrenal cortex.•GRM3 was detected in the zona glomerulosa of normal adrenal and idiopathic aldosteronism.•Treatment with the GRM3 agonist LY354740 decreased aldosterone/cortisol production in H295R cells.•Forskolin plus LY354740 resulted in decreased CYP11B1 and CYP11B2 mRNA compared to forskolin alone. 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. 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. 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. GRM3 is considered to regulate steroidogenesis in adrenocortical tissues.