Duparc Céline, Moreau Lucile, Dzib Jose Felipe Golib, Boyer Hadrien-Gaël, Tetsi Nomigni Milène, Boutelet Isabelle, Boulkroun Sheerazed, Mukai Kuniaki, Benecke Arndt G, Amar Laurence, Gobet Françoise, Meatchi Tchao, Plouin Pierre-François, Zennaro Maria-Christina, Louiset Estelle, Lefebvre Hervé
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.
J Clin Endocrinol Metab. 2015 Apr;100(4):E550-60. doi: 10.1210/jc.2014-3660. Epub 2015 Jan 19.
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.
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.
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.
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.
APA tissues commonly contain numerous mast cells that may influence aldosterone secretion through the local release of regulatory factors.
肾上腺肥大细胞可通过局部释放5-羟色胺（5-HT）和激活5-HT4受体来刺激醛固酮分泌。在醛固酮分泌性腺瘤（APA）中，5-HT4受体过度表达，对APA患者给予5-HT4受体激动剂可提高血浆醛固酮水平。这些数据以及肥大细胞在肿瘤发生中已被充分证明的作用表明，肥大细胞可能参与了APA的病理生理过程。
本研究旨在调查一系列APA组织中肥大细胞的存在情况，并研究肥大细胞对醛固酮分泌的影响。
采用免疫组织化学方法研究APA中肥大细胞的存在情况。将肥大细胞密度与临床数据进行比较。通过使用人肥大细胞和肾上腺皮质细胞系培养物来研究肥大细胞对醛固酮产生的影响。
与正常肾上腺相比，发现APA组织中肥大细胞密度增加。肥大细胞主要见于腺瘤附近的肾上腺皮质或腺瘤本身，据此区分出两组APA。发现一部分腺瘤含有高密度的肿瘤内肥大细胞，这与醛固酮合酶表达及体内醛固酮分泌参数相关。将人肥大细胞系培养物的条件培养基给予人肾上腺皮质细胞可导致醛固酮合酶（CYP11B2）mRNA表达和醛固酮产生显著增加。
APA组织通常含有大量肥大细胞，这些肥大细胞可能通过局部释放调节因子来影响醛固酮分泌。
