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

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.

Keywords: 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.