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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.
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Official URL: http://dx.doi.org/10.1152/ajpendo.00191.2013
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 | ||||||||
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | American Journal of Physiology: Endocrinology and Metabolism | ||||||||
| Publisher: | American Physiological Society | ||||||||
| ISSN: | 0193-1849 | ||||||||
| Official Date: | 1 November 2013 | ||||||||
| Dates: |
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| 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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