Dexamethasone inhibition of cyclooxygenase expression in bovine term placenta.
Since both prostaglandin (PG) F2 alpha and corticosteroids are elevated in mammals before the onset of parturition, we studied the effect of the synthetic corticosteroid dexamethasone on PGF2 alpha accumulation and cyclooxygenase (prostaglandin synthase, PGS) expression in the bovine fetal placenta. Cultures were prepared from cotyledons at different stages of gestation. The effect of dexamethasone on PGF2 alpha accumulation and PGS expression was determined by radioimmunoassay and [35S]methionine metabolic labeling followed by immunoprecipitation with specific anti-cyclooxygenase antibodies, respectively. Data demonstrate that in fetal placental cells at term, both PGF2 alpha accumulation and cyclooxygenase expression are significantly inhibited after 18 hours of dexamethasone treatment (150 nM). In contrast, neither first nor second trimester cells were sensitive to dexamethasone treatment. Dexamethasone inhibition of PGF2 alpha synthesis in fetal cells at term was abolished in the presence of RNA or protein synthesis inhibitors (actinomycin D or puromycin, 10 micrograms/ml each). Neither progesterone nor 17 beta-estradiol accumulation were affected by dexamethasone treatment at any stage of gestation. Data suggest that corticosteroids play a role in parturition through PGF2 alpha synthesis regulation by fetal placental cells. Since abnormalities during parturition e.g. retained placenta, are common following dexamethasone induction of labor in cows, we postulate that the local inhibition of PGF2 alpha accumulation by cotyledon cells after corticosteroid administration, may be involved in placental retention.
Izhar
M
M
Department of Hormone Research, Kimron Veterinary Institute, Beit Dagan, Israel.
Pasmanik
M
M
Marcus
S
S
Shemesh
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis*; D005260:Female; D007163:Immunosorbent Techniques; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D011863:Radioimmunoassay
D003609:Dactinomycin; D016718:Arachidonic Acid; D011691:Puromycin; D012313:RNA; D003907:Dexamethasone; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases