Control of Luteolytic Sensitivity in the Porcine Corpus Luteum

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Title: Control of Luteolytic Sensitivity in the Porcine Corpus Luteum
Author: Zorrilla, Leah
Advisors: John Gadsby, Committee Chair
Char Farin, Committee Member
Glen Almond, Committee Member
Rob Smart, Committee Member
Abstract: The porcine corpus luteum (CL) is unusual in that it does not show a luteolytic response to an exogenous dose of Prostaglandin F-2 (PGF-2 until after day 12 of an 18-21 day cycle, which is in marked contrast to other farm animal species in which luteolysis can be induced after about 6 days of the estrous cycle. The overall objective of these studies was to elucidate the mechanism by which the porcine CL acquires luteolytic sensitivity (LS=the ability to respond to PGF-2), which we hypothesized occurs between days 7 and 13 of the estrous cycle, and about which little is known. We examined the temporal patterns of expression and cellular localization of the Endothelin (ET)-1 system, Protein Kinase (PK)C isoforms, as well as genes associated with apoptosis at different stages of the estrous cycle to determine whether changes in expression correlated with the development of the acquisition of LS (i.e. between days 7-13. Additionally, we developed a cell culture system to investigate whether Tumor Necrosis Factor- (TNF-) was capable of sensitizing porcine luteal cells to PGF-2 in vitro, and thus whether it may play a role in development of LS in vivo. Our studies of expression of the ET-1 system components showed that Endothelin Converting Enzyme -1 (ECE-1) expression (protein) was increased on day 10 of the cycle, which would likely result in an increase production of active ET-1 peptide in the CL. Additionally, the results from the PKC study demonstrated that PKC  protein increased on day 13 (compared to day 7), suggesting that this particular PKC isoform may play a role in mediating the development of LS in the porcine CL. Furthermore, we showed that apoptosis-associated genes such as TNF-receptor I (TNFRI), p53 and iNOS⁄eNOS were expressed early (day 7) in the estrous cycle, suggesting the possibility that they may play also role in the acquisition of LS. Our in vitro data demonstrated that TNF- sensitized porcine luteal cells to PGF-2 in a dose dependent manner. TNF- also dose-dependently increased the expression of Endothelin Receptor A (ETA) and decreased PKC isoforms (II and ) in association with PGF-2 sensitivity. Overall, our in vivo and in vitro data are consistent with a working model in which TNF- (from infiltrating macrophages in the early CL) acts to increase ET-1 (via increased ECE-1) and ETA, resulting in increased expression of PKC , which enables luteal cells to become sensitive to the luteolytic effects of PGF-2.
Date: 2008-04-30
Degree: PhD
Discipline: Comparative Biomedical Sciences

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