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(Hypertension. 2001;38:1137.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Localization of the Endothelin System in Aldosterone-Producing Adenomas

Giorgia Egidy; Erno Baviera; Gladys Ciuffo; Pierre Corvol; Florence Pinet

From the INSERM Unit 36, Collège de France (G.E., P.C., F.P.), Paris, France; Service d’Anatamopathologie, Hopital Saint-Joseph (E.B.), Paris, France; and Catedra de Bioquimica Avanzada, Universidad Nacional de San Luis (G.C.), San Luis, Argentina.

Correspondence to Dr Florence Pinet, INSERM Unit 36, Collège de France, 11 place Marcellin Berthelol, 75005 Paris, France. E-mail florence.pinet{at}college-de-france.fr

Abstract—— Endothelin-1 (ET-1) could play a role in the regulation of aldosterone secretion of the human adrenal gland. The presence of the endothelin-converting enzyme 1 (ECE-1) and ET-1 suggests that there is a local ET system in the adrenal cortex, but the in situ synthesis of ET-1 remains to be confirmed. The cellular distribution of the whole ET system was evaluated in 20 cases of aldosterone-producing adenomas. Polymerase chain reaction studies gave strong signals for ECE-1 mRNA and the mRNAs for endothelin type A (ET_A) and B (ET_B) receptors and faint signals for prepro–ET-1 mRNA. In situ hybridization showed ET_A receptors scattered throughout the adenoma, in both secretory cells and vascular structures (score, +). There were more ET_B receptors (score, ++), but they were restricted mainly to the endothelium. ECE-1 mRNA and protein were ubiquitous and abundant in secretory cells (score, +++) and vascular structures (score, ++); the enzyme was active on big ET-1. There was no prepro–ET-1 mRNA in the cortex, except in the thickened precapillary arterioles present in only 30% of the aldosterone-producing adenomas studied. ET-1 immunoreactivity was detected in vascular structures (score, +), probably bound to receptors, suggesting that ET-1 has an endocrine action. The low concentrations of ET-1 could also indicate that it acts in a paracrine-autocrine fashion to control adrenal blood flow. The discrepancy between the concentrations of ECE-1 and its substrate suggests that ECE-1 has another role in the adrenal secretory cells. Our data indicate that ET probably is not a primary cause of the development or maintenance of the adenoma.

Key Words: endothelin • hypertension, endocrine • receptors, endothelin • regional blood flow • immunohistochemistry

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