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

Saulo J.A. Felizola, Yasuhiro Nakamura, Fumitoshi Satoh, Ryo Morimoto, Kumi Kikuchi, Tomohiro Nakamura, Atsushi Hozawa, Lin Wang, Yoshiaki Onodera, Kazue Ise, Keely M. McNamara, Sanae Midorikawa, Shinichi Suzuki, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalMolecular and Cellular Endocrinology
Issue number1
Publication statusPublished - 2014 Jan 25


  • Adrenal cortex
  • Adrenocortical adenoma
  • Aldosterone
  • CAMP
  • Glutamate receptor
  • Zona glomerulosa


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