OR02-4 Mast Cell Deficiency Causes Dysregulation of Aldosterone Secretion in Mice

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR02-Renin-Angiotensin-Aldosterone - Bench to Bedside
Basic/Translational
Friday, April 1, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:30 PM
Room 156 (BCEC)
Hadrien Gaël Boyer1, Julien Wils2, Arnaud Arabo3, Céline Duparc4, Isabelle Boutelet5, Herve Lefebvre*6 and Estelle Louiset7
1Inserm U982, Mont-Saint-Aignan, France, 2INSERM U982, Institute for Biomedical Research and Innovation, Mont Saint Aignan, France, 3Rouen University, Mont Saint Aignan, France, France, 4Inserm U982, Institute for Biomedical Research and Innovation, Mont Saint Aignan, France, 5Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen University, Mont-Saint-Aignan, France, 6INSERM U982, Rouen, France, 7INSERM U982, Institute for Biomedical Research and Innovation, University of Rouen, Mont Saint Aignan, France
We have previously shown that, in the human adrenal gland, aldosterone secretion is stimulated by subcapsular mast cells through local release of serotonin. In addition, mast cell conditioned medium increases CYP11B2 expression in the adrenocortical cell line H295R indicating that mast cells release factors which activate adrenal mineralocorticoid synthesis (1). Interestingly, the density of mast cells is increased in aldosterone-producing adenomas (APA). In the present study, we have investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 KitW-sh/W-sh mice in comparison with wild type (WT) C57BL/6 mice. In WT mice, adrenal mast cells located in the subcapsular region of the gland were activated by low sodium diet. KitW-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in WT animals but exhibited an increase in renal renin mRNA expression. Moreover, in mast cell-deficient mice, low sodium diet was unexpectedly found to induce an exaggerated aldosterone response which was associated with an increase in adrenal aldosterone synthase expression together with enlargement of zona glomerulosa. The enhancement of aldosterone production appeared to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was secondarily causative for an increase in systolic blood pressure and marked hypokalemia which favored polyuria. Activation of the adrenal renin-angiotensin system seems thus to represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Globally, these results suggest that mast cells play a significant role in the control of aldosterone secretion in mice. It will therefore be relevant to investigate aldosterone secretion in mouse strains displaying an increase in adrenal mast cell density, which may constitute valuable models for the study of the pathophysiology.

1)  Duparc C et al., J Clin Endocrinol Metab. 2015 100(4):E550-60.

(1) Duparc C et al. J Clin Endocrinol Metab. 2015; 100:E550-60.

Nothing to Disclose: HGB, JW, AA, CD, IB, HL, EL

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo

Sources of Research Support: Institut National de la Santé et de la Recherche Médicale, Conseil Régional de Haute-Normandie; Réseau LARC-Neuroscience