The effect of dexamethasone on CRH and prostanoid production from human term placenta.
The human placenta at term produces large quantities of corticotropin releasing hormone (CRH) and prostanoids. These hormones play an important role in the maintenance of pregnancy, and the initiation and progress of labor; yet little is known of factors affecting their regulation and the interrelationship of CRH and prostanoid production. In these studies we have investigated the effect of dexamethasone on the production of CRH and prostanoids from fresh human term placental tissues. The basal release of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) from human term placental explants increased from the fifth hour in culture, while the release of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) was not significantly changed during this period. The addition of dexamethasone (10(-8) M) to the perifusing medium resulted in a rapid and dramatic inhibition of PGE2, PGF2 alpha, PGFM, TxB2 and 6-keto-PGF1 alpha release. On the other hand, CRH release was not significantly changed throughout the seven hours of incubation with dexamethasone. These data demonstrate that glucocorticoids at physiologic concentrations can inhibit human term placental prostanoid production, and thus glucocorticoid production may play an important role in the physiological regulation of placental prostanoid production in the human placenta. However, dexamethasone did not alter CRH release, demonstrating that the inhibition of placental prostanoids by dexamethasone is not a CRH mediated event.
Siler-Khodr
T M
TM
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, USA.
Kang
I S
IS
Koong
M K
MK
Grayson
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007743:Labor, Obstetric; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000378:metabolism
D006063:Chorionic Gonadotropin; D005938:Glucocorticoids; D011453:Prostaglandins; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D015232:Dinoprostone