11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone stimulates chorionic gonadotropin secretion from human term cytotrophoblast cells differentiated in vitro

Am J Reprod Immunol. 2004 Aug;52(2):133-8. doi: 10.1111/j.1600-0897.2004.00195.x.

Abstract

Problem: To investigate the effect of altering local glucocorticoid concentration on human chorionic gonadotropin (hCG) production by cultured placental trophoblast cells.

Method of study: 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.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors*
  • Carbenoxolone / pharmacology*
  • Chorionic Gonadotropin / biosynthesis*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • Chorionic Gonadotropin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Carbenoxolone