Localization of the endothelin system in aldosterone-producing adenomas

Endothelin-1 (ET-1) could play a role in the regulation of aldosterone secr etion 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 s trong signals for ECE-1 mRNA and the mRNAs for endothelin type A (ETA) and B (ETB) receptors and faint signals for prepro-ET-1 mRNA. In situ hybridiza tion showed ETA receptors scattered throughout the adenoma, in both secreto ry cells and vascular structures (score, +). There were more ETB receptors (score, + +), but they were restricted mainly to the endothelium. ECE-1 mRN A 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 precap illary 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 act ion. The low concentrations of ET-1 could also indicate that it acts in a p aracrine-autocrine fashion to control adrenal blood flow. The discrepancy b etween the concentrations of ECE-1 and its substrate suggests that ECE-1 ha s another role in the adrenal secretory cells. Our data indicate that ET pr obably is not a primary cause of the development or maintenance of the aden oma.