Regulation of human trophoblast function by glucocorticoids: dexamethasone promotes increased secretion of chorionic gonadotropin.
Steroid hormones are thought to play a role in controlling placental endocrine function. Since maternal free cortisol levels increase during gestation, and glucocorticoid receptors have been identified in placental tissue, we examined the effects of glucocorticoids on the production of CG by cultured human cytotrophoblasts. Treatment of cytotrophoblasts with 1 microM dexamethasone increased CG secretion by 6- to 10-fold over a 72-h period, whereas progesterone (1 microM) had no effect. The stimulatory effects of dexamethasone were blocked by the glucocorticoid antagonist RU 486, indicating a requirement for the glucocorticoid receptor. Intracellular accumulation of the CG alpha-subunit in response to dexamethasone was demonstrated by immunocytochemistry, and Northern blot analyses revealed that dexamethasone treatment increases CG alpha- and beta-subunit mRNA levels. Dexamethasone also enhanced the stimulatory effects of 8-bromo-cAMP on CG secretion. We conclude that glucocorticoids as well as cAMP modulate human trophoblast endocrine functions.
Ringler
G E
GE
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104.
Kallen
C B
CB
Strauss
J F
JF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D006063:Chorionic Gonadotropin; D005938:Glucocorticoids; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D000242:Cyclic AMP