title: Prostaglandin F2alpha (PGF2alpha) independent and dependent regulation of the bovine luteal endothelin system.
abstract: We have examined the genes of the endothelin system that are targets for regulation by prostaglandin F2alpha (PGF2alpha). The effects of a luteolytic dose of PGF2alpha ) on the mRNA encoding endothelin converting enzyme-1 (ECE-1), pre-pro endothelin-1 (pp ET-1) and the ET receptors ETA, ETB, in bovine corpus luteum (CL) during the early (days 1 and 4), mid (day 10) or late (day 17) luteal phases were examined. The effect of the PGF(2alpha) treatment on ECE-1 protein, Big ET-1 and the biologically active mature ET-1 peptide were also examined. Most importantly, the direct ECE-1 activity was determined. Before day 10 of the cycle, in a PGF2alpha-independent manner, the amounts of mRNA encoding ET-1, ECE-1, ETA, and ETB were increased steadily from day 1. After day 10 of the cycle, expression of mRNA encoding pp ET-1 and ETA acquired responsiveness to exogenous PGF2alpha and both genes were up-regulated by the PGF2alpha treatment. This effect of PGF2alpha was also detected for the proteins corresponding to the mature ET-1. The enzymatic activity of ECE-1 remained unchanged throughout the lifespan of the CL in spite of the detected changes in mRNA and protein. The results suggest that the luteal endothelin system is regulated in a PGF2alpha-independent and -dependent manner. Importantly, an alteration in luteal ET-1 availability is most likely achieved by modulating the expression of mRNA encoding pp ET-1 and not by the amount or activity of ECE-1. This interpretation is supported by the observation that the activity of ECE-1 remained unchanged throughout the ovarian cycle. The combined effects of greater ET-1 availability and gene expression encoding the ETA receptor in the late luteal phase could render the CL, at this developmental stage, more sensitive or responsive to ET-1. If the luteal tissue is responsive to the available ET-1 during the early phase of the ovarian cycle, an additional role for ET-1 should be considered beyond mediating the luteolytic actions of PGF2alpha. Agents blocking the actions of ET-1 might be the best approach to interfere with the luteal ET system and test its physiological role(s) in vivo.
authors.affiliation: Department of Biology, West Virginia University, P.O. Box 6057, Morgantown, WV 26506-6057, USA.
authors.forename: Ekta
authors.initials: E
authors.lastname: Choudhary
authors.forename: Beth A
authors.initials: BA
authors.lastname: Costine
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wilson
authors.forename: E Keith
authors.initials: EK
authors.lastname: Inskeep
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Flores
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D003338:Corpus Luteum / Q000201:enzymology / Q000378:metabolism*; D015237:Dinoprost / Q000502:physiology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008666:Metalloendopeptidases; D012333:RNA, Messenger / Q000032:analysis; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D015237:Dinoprost; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes