Localization of the endothelin system in aldosterone-producing adenomas.
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.
Egidy
G
G
INSERM Unit 36, Collège de France, Paris, France.
Baviera
E
E
Ciuffo
G
G
Corvol
P
P
Pinet
F
F
D000302:Adrenal Cortex / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism*; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019332:Endothelin-1 / Q000276:immunology / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017466:Receptors, Endothelin / Q000096:biosynthesis* / Q000235:genetics
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012334:RNA, Neoplasm; D017466:Receptors, Endothelin; D000450:Aldosterone; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes