Prostaglandin F-2 alpha induces expression of prostaglandin G/H synthase-2 in the ovine corpus luteum: A potential positive feedback loop during luteolysis

The primary role of prostaglandin (PC) F-2 alpha in regression of the corpus luteum has been clearly demonstrated in many mammalian species. We have used in vivo and in vitro approaches to investigate the possibility that exogenous PGF(2 alpha) induces expression of prostaglandin G/H synthase-2 (PGHS-2; cyclooxygenase-2) and causes production of PGF(2 alpha) in ovine luteal cells. Ewes received infusions into the ovarian artery of 1 ml PGF(2 alpha) (1 mu mol) or saline, and corpora lutea were collected at various times and analyzed for PGHS-2 mRNA using quantitative, competitive reverse transcription polymerase chain reaction. PGF(2 alpha) dramatically increased the steady-state concentration of mRNA for PGHS-2 within 1 h, but basal concentration returned at 12 h posttreatment. In vitro studies using isolated ovine large luteal cells indicated that mRNA for PGHS-2 was induced by PGF(2 alpha), phorbol didecanoate, and ionomycin in a pattern similar to that observed in vivo. PGHS-2 protein was induced by all three treatments 4-12 h later, and accumulation of PGF(2 alpha) in the culture media increased at 12 and 24 h posttreatment. In conclusion, we have provided evidence that PGF(2 alpha), probably acting through the protein kinase C/free intracellular calcium pathway, can stimulate large luteal cells to express PGHS-2 and produce PGF(2 alpha), This luteal PGF(2 alpha) is likely to have an autocrine/paracrine function to augment the luteolytic effect of PGF(2 alpha) of uterine origin.