PMID- 12606425 OWN - NLM STAT- MEDLINE DCOM- 20040116 LR - 20220227 IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 68 IP - 4 DP - 2003 Apr TI - Hormonal regulation and cell-specific expression of endothelin-converting enzyme 1 isoforms in bovine ovarian endothelial and steroidogenic cells. PG - 1361-8 AB - Endothelin-converting enzyme 1 (ECE-1) is a key enzyme in the biosynthesis of endothelin 1 (ET-1), a potent regulator of ovarian function. Different ECE-1 isoforms are localized in distinct intracellular compartments. Thus, the spatial and temporal pattern of ECE-1 expression determines the site of big ET-1 activation and the bioavailability of ET-1. This study was undertaken to investigate the hormonal regulation and cell-specific expression of ECE-1 isoforms in endothelial and steroidogenic cells of bovine follicles and corpora lutea (CL). Using enriched follicular and luteal cell subpopulations and in situ hybridization techniques, we showed that the ECE-1 gene is expressed by both endothelial and steroidogenic cells; however, the intracellular ECE-1a isoform was present only in ET-1-expressing endothelial cells. Steroidogenic cells in follicles or in CL, deficient in ET-1, expressed only the plasma membrane ECE-1b isoform. The intensity of antisense ECE-1 labeling in the granulosa cell layer increased with follicular size; insulin-like growth factor I and insulin upregulated ECE-1 expression when cultured with granulosa cells, suggesting that these growth factors may increase ECE-1 in growing follicles. In contrast, ET-1 and LH downregulated ECE-1 in steroidogenic cells. This effect could account for low ECE (and ET-1) levels, which characterize the early luteal phase. These findings suggest that ECE-1 is regulated during different stages of the cycle in a physiologically relevant manner. The hormonal regulation and intracellular localization of bovine ECE-1 isoforms revealed in this study may provide new insights into ET-1 biosynthesis and mode of action in different cellular microenvironments within the ovary. FAU - Levy, Nitzan AU - Levy N AD - Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel. FAU - Gordin, Miri AU - Gordin M FAU - Smith, Michael F AU - Smith MF FAU - Bolden-Tiller, Olga U AU - Bolden-Tiller OU FAU - Meidan, Rina AU - Meidan R LA - eng PT - Journal Article DEP - 20021030 PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Endothelin-1) RN - 0 (Insulin) RN - 0 (Isoenzymes) RN - 0 (Steroids) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.71 (Endothelin-Converting Enzymes) SB - IM MH - Animals MH - Aspartic Acid Endopeptidases/*metabolism MH - Cattle MH - Cells, Cultured MH - Down-Regulation MH - Endothelin-1/metabolism/pharmacology MH - Endothelin-Converting Enzymes MH - Endothelium/cytology/drug effects/metabolism MH - Female MH - Insulin/*pharmacology MH - Insulin-Like Growth Factor I/*pharmacology MH - Isoenzymes/metabolism MH - Luteinizing Hormone/*pharmacology MH - Metalloendopeptidases MH - Ovarian Follicle/cytology/metabolism MH - Ovary/cytology/drug effects/*metabolism MH - Steroids/*biosynthesis MH - Up-Regulation EDAT- 2003/02/28 04:00 MHDA- 2004/01/17 05:00 CRDT- 2003/02/28 04:00 PHST- 2003/02/28 04:00 [pubmed] PHST- 2004/01/17 05:00 [medline] PHST- 2003/02/28 04:00 [entrez] AID - biolreprod.102.009134 [pii] AID - 10.1095/biolreprod.102.009134 [doi] PST - ppublish SO - Biol Reprod. 2003 Apr;68(4):1361-8. doi: 10.1095/biolreprod.102.009134. Epub 2002 Oct 30.