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.
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A Group II agonist acts on GRM3 receptors in adrenal gland cells, leading to a reduction in aldosterone and cortisol via inhibition of the adenylyl cyclase/cAMP signaling pathway.
“This same agonist has been shown to act on GRM3 (mGluR3) receptors in adrenal gland cells, leading to a reduction in aldosterone and cortisol via inhibition of the adenylyl cyclase/cAMP signaling pathway (Felizola et al., 2014).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Felizola et al., 2014
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Self-citation
- Authors
- Felizola, S. J. A., Nakamura, Y., Satoh, F., Morimoto, R., Kikuchi, K., Nakamura, T., Hozawa, A., Wang, L., Onodera, Y., Ise, K., McNamara, K. M., Midorikawa, S., Suzuki, S., & Sasano, H.
- Affiliations
- Tohoku University (JP)
- Tohoku University Hospital (JP)
- Harbin Medical University (CN)
- Fukushima Medical University (JP)
- Corresponding author
- Nakamura, Yasuhiro
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 382
- Issue
- 1
- Pages
- 170-177
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2005290724
- Cited by
- 30
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 9 · 2013: 1
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Takeda Science Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- glutamate receptors, steroidogenesis, adrenal cortex, aldosterone-producing adenoma, cortisol-producing adenoma, metabotropic glutamate receptors, GRM3, metabotropic glutamate receptor 1, angiotensin II, forskolin, LY354740, aldosterone, cortisol, idiopathic hyperaldosteronism, adrenocortical cells
- MeSH terms
- Cyclic AMP, Adrenal Glands, Aldosterone, Animals, Bridged Bicyclo Compounds, Humans, Hydrocortisone, Immunohistochemistry, Steroid 11-beta-Hydroxylase, Steroids, Time Factors, Blotting, Western, Signal Transduction, Polymerase Chain Reaction, Receptors, Metabotropic Glutamate, Cell Line, Tumor, Rats
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