Dexamethasone inhibition of prostaglandin production in human term placental cells is protein and ribonucleic acid synthesis dependent.
A key enzyme in the regulation of prostaglandin (PG) synthesis is PG synthase (PGS; cyclooxygenase), which converts arachidonic acid to PGs. Since both PGs and glucocorticoids are elevated before parturition, we studied the regulation of dexamethasone (DEX; 150 nM) on PGF2 alpha synthesis and PGS expression in human placental cells in vitro. Both first trimester and term placental cells were used. DEX reduced PGF2 alpha synthesis in human term placental cells, in contrast to first trimester cells which were unaffected by the same treatment. DEX inhibition of PGF2 alpha production by term placental cells was time and dose dependent. PGS expression was analyzed by [35S]methionine metabolic labeling and immunoprecipitation using polyclonal antibodies developed in rabbits against ram seminal vesicle PGS. DEX reduced PGS expression in term placental cells, but not in first trimester cells. In contrast to the effect of DEX on PGF2 alpha, progesterone and estradiol production by cells were unaffected at any stage of gestation examined. DEX inhibition of PGF2 alpha synthesis required de novo biosynthesis of RNA and proteins. These results suggest 1) corticosteroids play a role in the regulation of placental PG synthesis during parturition; 2) the inhibition of PG synthesis and PGS expression by glucocorticoids is RNA and protein biosynthesis dependent; and 3) induction of labor by glucocorticoids is not directly related to changes in placental progesterone or estradiol biosynthesis.
Pasmanik
M
M
Department of Hormone Research, Kimron Veterinary Institute, Beit Dagan, Israel.
Izhar
M
M
Zolti
M
M
Shemesh
M
M
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007743:Labor, Obstetric / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis*
D001095:Arachidonic Acids; D003609:Dactinomycin; D016718:Arachidonic Acid; D011691:Puromycin; D012313:RNA; D003907:Dexamethasone; D015237:Dinoprost