title: Mast cell hyperplasia is associated with aldosterone hypersecretion in a subset of aldosterone-producing adenomas.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  APA tissues commonly contain numerous mast cells that may influence aldosterone secretion through the local release of regulatory factors.
authors.affiliation: INSERM 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Duparc
authors.forename: Lucile
authors.initials: L
authors.lastname: Moreau
authors.forename: Jose Felipe Golib
authors.initials: JF
authors.lastname: Dzib
authors.forename: Hadrien-Gaël
authors.initials: HG
authors.lastname: Boyer
authors.forename: Milène
authors.initials: M
authors.lastname: Tetsi Nomigni
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boutelet
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
authors.forename: Arndt G
authors.initials: AG
authors.lastname: Benecke
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.forename: Françoise
authors.initials: F
authors.lastname: Gobet
authors.forename: Tchao
authors.initials: T
authors.lastname: Meatchi
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D046228:Microarray Analysis; D012189:Retrospective Studies
chemical_list: D000450:Aldosterone