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

• 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.

Nyckelord

Caspase 3

Caspases

metabolism

DNA Fragmentation

drug effects

Dexamethasone

pharmacology

Dihydrotestosterone

pharmacology

Electrophoresis

Agar Gel

Estrenes

pharmacology

Female

Furans

pharmacology

GABA Antagonists

pharmacology

Glucocorticoids

pharmacology

Granulosa Cells

cytology

drug effects

Hormone Antagonists

pharmacology

Humans

Mifepristone

pharmacology

Nucleosomes

drug effects

metabolism

Picrotoxin

pharmacology

Progesterone

pharmacokinetics

pharmacology

Receptors

GABA-A

deficiency

Receptors

Progesterone

antagonists & inhibitors

Spectrometry

Fluorescence

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