TY - JOUR
T1 - Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland
T2 - The metabotropic pathway
AU - Felizola, Saulo J.A.
AU - Nakamura, Yasuhiro
AU - Satoh, Fumitoshi
AU - Morimoto, Ryo
AU - Kikuchi, Kumi
AU - Nakamura, Tomohiro
AU - Hozawa, Atsushi
AU - Wang, Lin
AU - Onodera, Yoshiaki
AU - Ise, Kazue
AU - McNamara, Keely M.
AU - Midorikawa, Sanae
AU - Suzuki, Shinichi
AU - Sasano, Hironobu
N1 - Funding Information:
The first author received scholarship support from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
Funding Information:
This work was partially supported by the Takeda Science Foundation.
PY - 2014/1/25
Y1 - 2014/1/25
N2 - 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.
AB - 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.
KW - Adrenal cortex
KW - Adrenocortical adenoma
KW - Aldosterone
KW - CAMP
KW - Glutamate receptor
KW - Zona glomerulosa
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U2 - 10.1016/j.mce.2013.09.025
DO - 10.1016/j.mce.2013.09.025
M3 - Article
C2 - 24080311
AN - SCOPUS:84885409364
SN - 0303-7207
VL - 382
SP - 170
EP - 177
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1
ER -