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 increase in the metabolism of arachidonic acid or a specific increase in PG endoperoxide H synthase (PGHS) compared with lipoxygenase activities, and to determine intrauterine sites of these activities, we examined the metabolism of [3H]arachidonic acid by homogenates of placenta, amnion 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 content at the start of incubation was measured by capillary gas chromatography. Radioactive metabolites were separated and quantified by reverse-phase high-pressure liquid chromatography. At each gestational age arachidonic acid was converted to PGs, leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs). Conversion to PGs was greater in amnion than in chorion or placenta between days 78 and 140. The formation of PGs rose in placenta at term to a mean value twice that of amnion and ten times that of chorion. In amnion, the ratio of PG:LT rose significantly at term relative to 100-140 days of gestation. In placenta, the ratio of PG:LT produced from arachidonic acid and the ratio of total PGHS:lipoxygenase products rose significantly at term. In the day-125 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 significantly in the chorion and the placenta relative to controls. In both the placenta and the amnion there was a significant increase in the ratio 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 there is a preferential increase in the formation of PGs over lipoxygenase products. These results are consistent with the suggestion that there is an increase in the expression or activity of PGHS in the placenta of sheep in late pregnancy.
Langlois
D A
DA
Lawson Research Institute, St Joseph's Health Centre, London, Ontario, Canada.
Fraher
L J
LJ
Khalil
M W
MW
Fraser
M
M
Challis
J R
JR
D000650:Amnion / Q000201:enzymology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis; D008084:Lipoxygenase / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D011453:Prostaglandins; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D006854:Hydrocortisone