Mifepristone attenuates human chorionic gonadotropin-induced extracellular signal-regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells.
OBJECTIVE
To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction.


METHODS
An in vitro study.


METHODS
University hospital.


METHODS
Our subjects were women under the age of 40 who were unable to get pregnant as a result of male-factor infertility.


METHODS
HCG and RU486 were added to cultured granulosa luteal cells; after incubation for 12 hours, the harvested cells were subjected to total mRNA and protein measurements.


METHODS
Reverse transcriptase-polymerase chain reaction, immunoblot assay, immunocytochemistry, and enzyme immunoassay were performed.


RESULTS
RU486 attenuates hCG-induced cyclooxygenase-2 (COX-2) mRNA and protein expression and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and decreases the hCG-induced prostaglandin E2 (PGE2) production in a dose-dependent manner. RU486 treatment had no significant effect on COX-1 mRNA expression.


CONCLUSIONS
Treatments using gonadotropins are able to induce ERK1/2 phosphorylation resulting in increased COX-2 protein expression and prostaglandin synthesis. RU486 attenuates the activation of ERK1/2, decreases the expression of COX-2, and affects PGE2 production by inhibiting hCG-induced COX-2 expression.
Tsai
Eing-Mei
EM
Department of Obstetrics and Gynecology, Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan, Republic of China.
Chan
Te-Fu
TF
Chen
Yung-Hung
YH
Hsu
Shih-Cheng
SC
Chuang
Chiao-Ya
CY
Lee
Jau-Nan
JN
D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one