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

Journal article
Authors Eva Ch Svensson
Emilia Markström
Linus Ruijin Shao
Madeleine Andersson
Håkan Billig
Published in Fertility and sterility
Volume 76
Issue 6
Pages 1225-31
ISSN 0015-0282
Publication year 2001
Published at Institute of Clinical Neurosciences, Section of Ophtalmology
Institute of Physiology and Pharmacology
Institute of Physiology and Pharmacology, Dept of Physiology
Pages 1225-31
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords 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
Subject categories Medical and Health Sciences

Abstract

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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