Exogenous prostaglandins (PGs) have been reported to suppress or to promote the function of the primate corpus luteum in vitro and in vivo, but the role of endogenous ovarian prostaglandins in regulating luteal function during the menstrual cycle is unknown. Infusion (via osmotic pump) of the prostaglandin-synthesis inhibitor sodium meclofenamate into the corpus luteum, but not via the jugular vein, during the midluteal phase of the menstrual cycle resulted in a decline in progesterone levels and premature menses in rhesus monkeys (Macaca mulatta). These results suggest that meclofenamate suppresses the production of an obligatory luteotropic prostaglandin or other metabolite of arachidonic acid. We were unable to confirm that ovarian prostaglandin synthesis was diminished during treatment, since we could not consistently measure a gradient in PGE or PGF₂(α) across the ovary. Dispersed cells from the macaque corpus luteum produced PGF₂(α) in vitro. Production was stimulated by exposure to arachidonic acid and was inhibited by meclofenamate and another prostaglandin-synthesis inhibitor, flurbiprofen. Although the two drugs were potent inhibitors of prostaglandin synthesis in vitro, intraluteal infusion of flurbiprofen in monkeys did not mimic the luteolytic effects of meclofenamate. These studies provide the first evidence of an obligatory luteotropic role for a metabolite of arachidonic acid during the primate luteal phase. However the data suggest that the luteolytic effect of meclofenamate in vivo is not mediated entirely by the inhibition of local prostaglandin synthesis. Further studies are needed to determine the mechanism(s) of meclofenamate-induced luteolysis and to identify the putative obligatory luteotropin.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/184406 |
| Date | January 1988 |
| Creators | Sargent, Eva Lee. |
| Contributors | Stouffer, Richard |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Dissertation-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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