Cellular distribution of endothelin-converting enzyme-1 in human tissues

J Histochem Cytochem. 1999 Apr;47(4):447-62. doi: 10.1177/002215549904700403.

Abstract

Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin biosynthesis, catalyzing the final processing step. As shown by the targeted disruption of the ECE-1 gene, mature endothelins must be produced at specific sites for normal embryonic development. Therefore, it is important to know the exact pattern of ECE-1 gene expression. In this study we investigated the cellular distribution of ECE-1 in a variety of human tissues by in situ hybridization and immunohistochemistry. Widespread expression of the ECE-1 gene was noted, with a similar distribution pattern for mRNA and protein in normal human tissues, suggesting a major biological role for ECE-1. ECE-1 levels were particularly high in the cardiovascular, reproductive, and endocrine systems. There was strong and consistent labeling for ECE-1 in the vascular endothelial cells of all organs examined and in various nonvascular cells, especially some glandular cells. A large amount of ECE-1 protein and mRNA was detected in the Leydig cells of the testis and in the granulosa and theca cells of the ovary. In the adrenal gland, ECE-1 was detected in the cortex and medulla, with the strongest labeling in the zona glomerulosa. Therefore, ECE-1 may be involved in other systems, such as the regulation of hormone secretion, rather than exclusively generating ET-1 from its precursor. These results point out the potential side effects of ECE-1 inhibitors that are currently under development for treatment of cardiovascular diseases. (J Histochem Cytochem 47:447-461, 1999)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Specificity
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism*
  • Child
  • Child, Preschool
  • Digestive System / metabolism
  • Endocrine Glands / metabolism
  • Endothelin-Converting Enzymes
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Infant
  • Infant, Newborn
  • Lymphoid Tissue / metabolism
  • Male
  • Metalloendopeptidases
  • Middle Aged
  • RNA, Messenger / metabolism
  • Respiratory System / metabolism
  • Tissue Distribution
  • Urogenital System / metabolism

Substances

  • RNA, Messenger
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • ECE1 protein, human
  • Endothelin-Converting Enzymes