ESPE Abstracts (2018) 89 P-P1-013

Role of Mast Cells in the Establishment of the Mineralocorticoid Pathway in the Developing Mouse

Alexandre Naccachea, Estelle Louiseta, Antonin Lamaziereb, Michael Thomasa, Arnaud Araboa, Hervé Lefebvrea & Mireille Castaneta

aNormandie Univ, UNIROUEN, INSERM, U1239, Laboratory of Differentiation & Neuronal and Neuroendocrine Communication, Institute for Research and Innovation in Biomedicine, Rouen, France; bERL INSERM 1157/UMR7203, Paris, France

Mast cells are known to control mineralocorticoid synthesis and secretion in human normal adrenal gland and aldosterone-producing adenomas through release of serotonin. We recently detected these immune cells in human fetal adrenal from 18 weeks of gestation in the subcapsular layer, in correlation with the expression of steroidogenic enzymes required for aldosterone biosynthesis. This observation suggests the implication of mast cells in the mineralocorticoid synthesizing pathway during adrenal development. To test this hypothesis, we investigated the impact of the absence of mast cells on mineralocorticoid enzymes expression and on perinatal aldosterone secretion in mouse models. Using Q-PCR, we studied at different stages of perinatal development (E18, E20, P0, P1, P3) adrenal-kidney complexes obtained from either mast cell-deficient KitW-sh/W-sh versus wild type (WT) C57BL/6 mice. Aldosterone plasma levels were also quantified in neonates at P0 and P1using tandem mass spectrometry in both models. RT-QPCR revealed lower Cyp11b2 mRNA levels in KitW-sh/W-sh than WT animals during fetal and post-natal development. By contrast, Cyp21a1 and Hsd3b1 mRNAs levels were similar in both models. Moreover, aldosterone levels were significantly lower in KitW-sh/W-sh compared to wild type mice at P0 and P1. Altogether, these data strongly suggest a role of mast cells in perinatal mineralocorticoid pathway in mice. In conclusion, we here demonstrated the implication of mast cells in the establishment and control of the mineralocorticoid function in fetal and post-natal development in mice. Further studies are now required to better understand the pathophysiology of the perinatal aldosterone production in mouse models as well as in humans, in order to better manage the salt wasting syndrome disorder in extreme premature infants.

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