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Published on: May 23, 2014
Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells
E C Svensson1, E Markström, R Shao
1Department of Physiology, Göteborg University, Göteborg, Sweden.
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:
Göteborg 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 microM-100 microM), Org 31710 (1 microM-100 microM), progesterone (1 nM-10 microM), dexamethasone (0.5 microM-100 microM), dihydrotestosterone (1 nM-25 microM), RU 486 (10 microM-100 microM) + dexamethasone (50 microM), and picrotoxin (1 microM-100 microM) 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.
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