Distinct cellular localization and regulation of endothelin-1 and endothelin-converting enzyme-1 expression in the bovine corpus luteum: Implicationsfor luteolysis

Endothelin-1 (ET)-1 within the corpus luteum (CL) is rapidly up-regulated d uring natural or PGF(2 alpha)-induced luteolysis; however, such an increase was not observed at early luteal stage when the CL is refractory to PGF(2 alpha). The mature and active form of ET-1 is derived from the inactive int ermediate peptide, big ET-1, by ET-converting enzyme (ECE)-1. This study th erefore examined the developmental and cell-specific expression of ECE-1 in bovine CL. A significant, 4-fold, elevation in ECE-1 expression (mRNA and protein levels) occurred during the transition of the CL from early to midl uteal phase. Analysis using in-situ hybridization and enriched luteal cell subpopulations showed that both steroidogenic and endothelial cells of the CL expressed high levels of ECE-1 mRNA, prepro ET-1 mRNA, on the other hand , was only expressed by resident endothelial cells. These data suggest that luteal parenchymal and endothelial cells may cooperate in the biosynthesis of mature bioactive ET-1. In the mature CL, ECE-1 mRNA increase occurred b oth in steroidogenic and endothelial cells and was accompanied by a signifi cant rise in ET-1 peptide. However, in contrast to ECE-1, prepro ET-1 mRNA levels were similar in early and midluteal-phase CL. Low ECE-1 levels durin g the early luteal phase, restricting the production of active ET-1, may ex plain why the immature CL is able to withstand PGF(2 alpha)-induced luteoly sis.