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QRFP induces aldosterone production via PKC and T-type calcium channel-mediated pathways in human adrenocortical cells : evidence for a novel role of GPR 103

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Ramanjaneya, Manjunath, Karteris, Emmanouil, Chen, Jing, Rucinski, R., Ziolkowska, A., Ahmed, Naila, Kagerer, S., Johren, O., Lehnert, Hendrik, Malendowicz, L. K. and Randeva, Harpal S. (2013) QRFP induces aldosterone production via PKC and T-type calcium channel-mediated pathways in human adrenocortical cells : evidence for a novel role of GPR 103. American Journal of Physiology: Endocrinology and Metabolism, 305 (9). E1049-E1058. ISSN 0193-1849.

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Official URL: http://dx.doi.org/10.1152/ajpendo.00191.2013

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Abstract

Hormonal regulation of adrenal function occurs primarily through activation of GPCRs. GPCRs are central to many of the body's endocrine and neurotransmitter pathways. Recently, it was shown that activation of GPR103 by its ligand QRFP induced feeding, locomotor activity, and metabolic rate, and QRFP is bioactive in adipose tissue of obese individuals. Given that the adrenal gland is a pivotal organ for energy balance and homeostasis, we hypothesized that GPR103 and QRFP are involved in steroidogenic responses. Using qRT-PCR and immunohistochemistry, we mapped both GPR103 and QRFP in human fetal and adult adrenal gland as well as rat adrenals. Both were primarily localized in the adrenal cortex but not in the medulla. Activation of GPR103 in human adrenocortical H295R cells led to a decrease in forskolin-increased cAMP and an increase of intracellular Ca(2+) levels. In addition, treatment of H295R cells with QRFP induced aldosterone and cortisol secretion as measured by ELISA. These increases were accompanied by increased expression and activity of StAR, CYB11B1, and CYP11B2 as assessed by qRT-PCR and luciferase reporter assay, respectively. Using specific inhibitors, we also demonstrated that aldosterone induction involves MAPK, PKC, and/or T-type Ca(2+) channel-dependent pathways. These novel data demonstrate that QRFP induces adrenal steroidogenesis in vitro by regulating key steroidogenic enzymes involving MAPK/PKC and Ca(2+) signaling pathways.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: American Journal of Physiology: Endocrinology and Metabolism
Publisher: American Physiological Society
ISSN: 0193-1849
Official Date: 1 November 2013
Dates:
DateEvent
1 November 2013Published
14 August 2013Accepted
5 April 2013Submitted
Volume: 305
Number: 9
Page Range: E1049-E1058
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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