Date of Graduation

2005

Document Type

Thesis

Degree Type

MS

Committee Chair

Jorge A. Flores

Abstract

The genes of the endothelin system are the potential targets for regulation by prostaglandin F2α (PGF2α) and have been studied in greater detail. The effects of a luteolytic dose of PGF2α on the mRNA encoding endothelin converting enzyme-1 (ECE1), pre-pro endothelin-1 (ET-1) and the ET receptors ETA, ETB, and in bovine corpus luteum (CL) collected during the early, mid or late luteal phases were examined. The effects of treatment with PGF2α on ECE-1 protein, big ET-1 and the biologically active mature ET-1 were examined. Most importantly, the direct activity of ECE-1 was determined. Based on the results it is suggested that the luteal endothelin system is regulated in both PGF2α -independent and -dependent manners. During the PGF2αindependent regulated phase (before day 10 of the cycle), the amounts of mRNA encoding ET-1, ECE-1, ETA, and ETB were steadily increased from day 1. During the PGF2α-dependent phase, expression of mRNA encoding ppET-1 and ETA acquired responsiveness to exogenous PGF2α. Both ppET-1 and ETA were up-regulated by treatment with PGF2α. This effect of PGF2α was detected for the proteins corresponding to the mature ET-1. The ECE-1 activity remained unchanged throughout the lifespan of the CL, in spite of the detected changes in mRNA and protein. Collectively, it is suggested from these data that an alteration in luteal ET-1 availability is achieved by modulating the expression of ppET-1 and that the action of ECE-1 is not the rate-limiting

step in this process. This interpretation is supported by the observation that the activity of ECE-1 remained unchanged throughout the ovarian cycle. In fact, the ECE-1 gene appears to be constitutively expressed until the final phase of the lifespan of the CL, when the gene appears to be down regulated. 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 PGF2α. Agents blocking the actions of ET-1 might be the best approach to interfere with the luteal ET system and test its physiological(s) role in vivo.

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