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Regulation of aldosterone secretion by mineralocorticoid receptor–mediated signaling

Authors :
Anis Amalina Abdul Hamid
Luminita H. Pojoga
Gordon H. Williams
Amanda E Garza
Cherish Chong
Jose R. Romero
Gail K. Adler
Tham M. Yao
Source :
Journal of Endocrinology. 232:525-534
Publication Year :
2017
Publisher :
Bioscientifica, 2017.

Abstract

We posit the existence of a paracrine/autocrine negative feedback loop, mediated by the mineralocorticoid receptor (MR), regulating aldosterone secretion. To assess this hypothesis, we asked whether altering MR activity in zona glomerulosa (ZG) cells affects aldosterone production. To this end, we studiedex vivoZG cells isolated from male Wistar rats fed chow containing either high (1.6% Na+(HS)) or low (0.03% Na+(LS)) amount of sodium. Western blot analyses demonstrated that MR was present in both the ZG and zona fasciculata/zona reticularis (ZF/ZR/ZR). In ZG cells isolated from rats on LS chow, MR activation by fludrocortisone produced a 20% and 60% reduction in aldosterone secretion basally and in response to angiotensin II (ANGII) stimulation, respectively. Corticosterone secretion was increased in these cells suggesting that aldosterone synthase activity was being reduced by fludrocortisone. In contrast, canrenoic acid, an MR antagonist, enhanced aldosterone production by up to 30% both basally and in response to ANGII. Similar responses were observed in ZG cells from rats fed HS. Modulating glucocorticoid receptor (GR) activity did not alter aldosterone production by ZG cells; however, altering GR activity did modify corticosterone production from ZF/ZR/ZR cells both basally and in response to adrenocorticotropic hormone (ACTH). Additionally, activating the MR in ZF/ZR/ZR cells strikingly reduced corticosterone secretion. In summary, these data support the hypothesis that negative ultra-short feedback loops regulate adrenal steroidogenesis. In the ZG, aldosterone secretion is regulated by the MR, but not the GR, an effect that appears to be secondary to a change in aldosterone synthase activity.

Details

ISSN :
14796805 and 00220795
Volume :
232
Database :
OpenAIRE
Journal :
Journal of Endocrinology
Accession number :
edsair.doi.dedup.....65469307994533e0df4bed952809d63a