title: Hormonal regulation and cell-specific expression of endothelin-converting enzyme 1 isoforms in bovine ovarian endothelial and steroidogenic cells.
abstract: 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.
authors.affiliation: Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Levy
authors.forename: Miri
authors.initials: M
authors.lastname: Gordin
authors.forename: Michael F
authors.initials: MF
authors.lastname: Smith
authors.forename: Olga U
authors.initials: OU
authors.lastname: Bolden-Tiller
authors.forename: Rina
authors.initials: R
authors.lastname: Meidan
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008666:Metalloendopeptidases; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D007328:Insulin; D007527:Isoenzymes; D013256:Steroids; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes