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Regulation of aldosterone secretion by mineralocorticoid receptor–mediated signaling
- 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.
- Subjects :
- Male
0301 basic medicine
Aldosterone synthase
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Article
03 medical and health sciences
chemistry.chemical_compound
Receptors, Glucocorticoid
0302 clinical medicine
Endocrinology
Mineralocorticoid receptor
Zona fasciculata
Corticosterone
Internal medicine
medicine
Animals
Rats, Wistar
Aldosterone
biology
Adrenal cortex
Sodium, Dietary
Zona Reticularis
Rats
Receptors, Mineralocorticoid
030104 developmental biology
medicine.anatomical_structure
chemistry
Zona glomerulosa
biology.protein
Zona Glomerulosa
Zona reticularis
Signal Transduction
Subjects
Details
- ISSN :
- 14796805 and 00220795
- Volume :
- 232
- Database :
- OpenAIRE
- Journal :
- Journal of Endocrinology
- Accession number :
- edsair.doi.dedup.....65469307994533e0df4bed952809d63a