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Does prostaglandin F2alpha released from the uterus by oxytocin mediate the oxytocic action of oxytocin?

The role of prostaglandin F20 (PGF20) in the oxytocic response to oxytocin (OT) was investigated by infusing OT directly into the uterine artery of the sheep and recording changes in both the pattern of uterine motility and the rate of secretion of PGF20 at different stages of the estrous cycle. On Day 3 (estrus = Day 0), OT infused from 0.1 to 5.0 mU/mm produced a dose-related increase in the rate of secretion of PGF20 but increased intrauterine pressure (IUP) and the frequency of contractions only at intermediate (1 mU/mm) or high (5 mU/mm) doses. Although exogenous PGF20 infused at 15 Mg/h mimicked OT, the myometrium responded normally to OT when the production of endogenous PGF20 was suppressed with indomethacin. On Day 8, an intermediate dose of OT changed neither the pattern of uterine motility nor the rate of secretion of PGF20. On Day 14, OT infused at rates as low as 0.025 mU/mm increased the secretion of PGF20 4-fold but induced no change in IUP or frequency of contraction. At 0.1 mU/mm, OT increased the rate of secretion of PGF20 nearly 10-fold within 3 mm but changed IUP only slightly and after a delay of 5 mm. Even at higher doses, OT invariably elevated PGF20 secretion but did not consistently raise IUP. We conclude that while increased contractile activity is not a sine qua non for OT-induced synthesis of PGF20, neither is increased synthesis of PGF20 an essential intermediate step in the activation of the myometrium by OT.