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Published on: September 15, 2017
Mast cell hyperplasia is associated with aldosterone hypersecretion in a subset of aldosterone-producing adenomas
Céline Duparc1, Lucile Moreau, Jose Felipe Golib Dzib
1INSERM Unité 982 (C.D., L.M., H.-G.B., M.T.N., I.B., E.L., H.L.) and Institute for Research and Innovation in Biomedecine (C.D., L.M., H.-G.B., M.T.N., I.B., E.L., H.L.), Normandie Université, 76821 Mt St Aignan, France; Laboratory of Neuronal and Neuroendocrine Differenciation and Communication (C.D., L.M., H.-G.B., M.T.N., I.B., E.L., H.L.), Université de Rouen, 76821 Mt St Aignan, France; Departments of Endocrinology (L.M., H.L.) and Pathology (F.G.), Institute for Research and Innovation in Biomedecine, University Hospital of Rouen, 76031 Rouen, France; Institut des Hautes Etudes Scientifiques (J.F.G.D., A.G.B.), Centre National de la Recherche Scientifique, 91440 Bures sur Yvette, France; INSERM (S.B., L.A., T.M., P.-F.P., M.-C.Z.), Unité Mixte de Recherche en Santé 970, Paris Cardiovascular Research Center, 75015 Paris, France; Université Paris Descartes (S.B., L.A., T.M., P.-F.P., M.-C.Z.), Sorbonne Paris Cité, 75015 Paris, France; Department of Biochemistry (K.M.), School of medicine, Keio University, Tokyo 160-8582, Japan; and Assistance Publique-Hôpitaux de Paris (L.A., T.M., P.-F.P., M.-C.Z.), Hôpital Européen Georges Pompidou, 75098 Paris, France.
Context:
Adrenal mast cells can stimulate aldosterone secretion through the local release of serotonin (5-HT) and activation of the 5-HT4 receptor (5-HT4). In aldosterone-producing adenomas (APAs), 5-HT4 receptor is overexpressed and the administration of 5-HT4 receptor agonists to patients with APA increases plasma aldosterone levels. These data and the well-documented role of mast cells in tumorigenesis suggest that mast cells may be involved in the pathophysiology of APA.
Objective:
The study aimed at investigating the occurrence of mast cells in a series of APA tissues and to examine the influence of mast cells on aldosterone secretion.
Design:
The occurrence of mast cells in APAs was investigated by immunohistochemistry. Mast cell densities were compared with clinical data. The influence of mast cells on aldosterone production was studied by using cultures of human mast cell and adrenocortical cell lines.
Results:
In APA tissues, the density of mast cells was found to be increased in comparison with normal adrenals. Mast cells were primarily observed in adrenal cortex adjacent to adenomas or in the adenomas themselves, distinguishing two groups of APAs. A subset of adenomas was found to contain a high density of intratumoral mast cells, which was correlated with aldosterone synthase expression and in vivo aldosterone secretory parameters. Administration of conditioned medium from cultures of human mast cell lines to human adrenocortical cells induced a significant increase in aldosterone synthase (CYP11B2) mRNA expression and aldosterone production.
Conclusion:
APA tissues commonly contain numerous mast cells that may influence aldosterone secretion through the local release of regulatory factors.
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