11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone stimulates chorionic gonadotropin secretion from human term cytotrophoblast cells differentiated in vitro.
OBJECTIVE
To investigate the effect of altering local glucocorticoid concentration on human chorionic gonadotropin (hCG) production by cultured placental trophoblast cells.


METHODS
Human placental trophoblasts were isolated from fresh placentas. Cytotrophoblasts were purified and placed into 24-well multiplates. For cultivation Dulbecco's modified Eagle's medium (DMEM) with 15 mm HEPES and 15% FBS was used. 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) activity and its inhibition by carbenoxolone (CE) were measured in cultured cells. Cultures were exposed to CE for 16-20 hr. Overnight production of hCG was measured by radioimmunoassay in control and treated cells.


RESULTS
The 11beta-HSD activity in these cultures was inhibited by nm concentrations of CE, the apparent Ki being 2.5 nm. Inhibition of 11beta-HSD activity with 0.1 nm CE resulted in 1.5-fold increase in the production of hCG.


CONCLUSIONS
Increasing local glucocorticoid concentration by the inhibition of 11beta-HSD results in higher hCG secretion, which in turn enhance cell differentiation.
Nacharaju
Vijaya L
VL
Department of Obstetrics and Gynecology, Down State Medical Center, SUNY, Brooklyn, NY, USA.
Divald
Andras
A
McCalla
Cyrus O
CO
Yang
Lianfu
L
Muneyyirci-Delale
Ozgul
O
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors*; D002229:Carbenoxolone / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002229:Carbenoxolone