Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells

Autor: Emilia Markström, Ruijin Shao, Eva Ch Svensson, Madeleine Andersson, Håkan Billig
Rok vydání: 2001
Předmět:
Zdroj: Fertility and Sterility. 76:1225-1231
ISSN: 0015-0282
DOI: 10.1016/s0015-0282(01)02891-6
Popis: Objective: To investigate if progesterone receptor (PR)-mediated effects are involved in regulating the susceptibility to apoptosis in LH receptor-stimulated human luteinizing granulosa cells. Design: Laboratory study. Setting: Goteborg University and an in vitro fertilization laboratory of a university hospital. Patient(s): Women undergoing oocyte retrieval for in vitro fertilization after ovulation induction with gonadotropins. Intervention(s): Luteinizing granulosa cells were isolated from follicular aspirates after oocyte removal. The cells were treated with or without RU 486 (1 μM–100 μM), Org 31710 (1 μM–100 μM), progesterone (1 nM–10 μM), dexamethasone (0.5 μM–100 μM), dihydrotestosterone (1 nM–25 μM), RU 486 (10 μM–100 μM) + dexamethasone (50 μM), and picrotoxin (1 μM–100 μM) and were cultured under serum-free conditions. Main Outcome Measure(s): Measurement of caspase-3 activity; detection of internucleosomal DNA fragmentation using gel electrophoresis and fluorospectrophotometry; progesterone analysis of spent medium. Result(s): Addition of the PR antagonists RU 486 or Org 31710 in vitro to human luteinizing granulosa cells caused an increase in caspase-3 activity and a dose-dependent increase in internucleosomal DNA fragmentation. No effect on DNA fragmentation was seen after addition of dexamethasone, dihydrotestosterone, or picrotoxin . Conclusion(s): Nuclear PR-mediated effects are involved in regulating the susceptibility to apoptosis in LH receptor-stimulated human luteinizing granulosa cells.
Databáze: OpenAIRE