Trophoblastic and decidual response to RU486: effects on human chorionic gonadotrophin, human placental lactogen, prolactin and pregnancy-associated plasma protein-A production in vitro.
RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha- (prop-1-ynyl)-oestra-4,9-dien-3-one] a potent progesterone antagonist, was shown to induce abortions in humans. Human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein-A (PAPP-A) decreased after RU486 administration, but it was not clear whether these effects were due to RU486 or secondary to trophoblast damage. To answer this question we tested the in-vitro effects of RU486 on short-term cultures of trophoblastic and decidual explants. It was observed that RU486 induced a significant inhibition of the trophoblastic production rate of beta HCG and PAPP-A but not human placental lactogen. This effect could be overcome by addition of progesterone (for PAPP-A and beta HCG) or cortisol (for beta HCG). Decidual prolactin (Prl) or PAPP-A secretions were also inhibited by RU486. Progesterone antagonized these effects, whereas cortisol was ineffective. These results suggest that PAPP-A is a progesterone-dependent protein and that the abortifacient effect of RU486 in humans could at least partially be due to an inhibition of the production of HCG and/or PAPP-A.
Bischof
P
P
Department of Obstetrics and Gynecology, University of Geneva, Switzerland.
Sizonenko
M T
MT
Herrmann
W L
WL
D000019:Abortifacient Agents / Q000494:pharmacology*; D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D018997:Chorionic Gonadotropin, beta Subunit, Human; D003470:Culture Media; D003656:Decidua / Q000187:drug effects*; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015735:Mifepristone; D010446:Peptide Fragments / Q000096:biosynthesis; D010928:Placental Lactogen / Q000096:biosynthesis; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis / Q000378:metabolism; D011372:Progestins / Q000037:antagonists & inhibitors*; D011388:Prolactin / Q000096:biosynthesis / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D014327:Trophoblasts / Q000187:drug effects*
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D003470:Culture Media; D004963:Estrenes; D010446:Peptide Fragments; D011372:Progestins; D015735:Mifepristone; D011388:Prolactin; D010928:Placental Lactogen; D011266:Pregnancy-Associated Plasma Protein-A