PREFERENTIAL INCREASE IN PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE COMPARED WITH LIPOXYGENASE ACTIVITY IN SHEEP PLACENTA AND AMNION AT TERM PREGNANCY AND AFTER INTRAFETAL GLUCOCORTICOID ADMINISTRATION

Prostaglandins (PGs) have been implicated as stimulants to myometrial contractility at parturition in many species. To determine whether the increased production of PGs at parturition reflects a general increas e in the metabolism of arachidonic acid or a specific increase in PG e ndoperoxide H synthase (PGHS) compared with lipoxygenase activities, a nd to determine intrauterine sites of these activities, we examined th e metabolism of [H-3]arachidonic acid by homogenates of placenta, amni on and chorion from sheep at days 78-80, 100-105, 135-140 of pregnancy and at term (day 145). Tissues were also obtained from fetuses at day 125; four of these were infused for 84 h with cortisol and four were used as saline-treated controls. The endogenous arachidonic acid conte nt at the start of incubation was measured by capillary gas chromatogr aphy. Radioactive metabolites were separated and quantified by reverse -phase high-pressure liquid chromatography. At each gestational age ar achidonic acid was converted to PGs, leukotrienes (LTs) and hydroxyeic osatetraenoic acids (HETEs). Conversion to PGs was greater in amnion t han in chorion or placenta between days 78 and 140. The formation of P Gs rose in placenta at term to a mean value twice that of amnion and t en times that of chorion. In amnion, the ratio of PG : LT rose signifi cantly at term relative to 100-140 days of gestation. In placenta, the ratio of PG : LT produced from arachidonic acid and the ratio of tota l PGHS:lipoxygenase products rose significantly at term. In the day-12 5 fetuses treated with cortisol there was a significant increase in PG production relative to that in control fetuses infused with saline in placenta, amnion and chorion; the placenta and amnion being the major sites of PG production. Production of LTs and HETEs also rose signifi cantly in the chorion and the placenta relative to controls. In both t he placenta and the amnion there was a significant increase in the rat io of total PGHS to lipoxygenase products formed. We conclude that at term labour and in labour induced by intrafetal cortisol infusion, the placenta is the major site of arachidonic acid metabolism, and that t here is a preferential increase in the formation of PGs over lipoxygen ase products. These results are consistent with the suggestion that th ere is an increase in the expression or activity of PGHS in the placen ta of sheep in late pregnancy.