Document Detail


Preantral follicle growth is regulated by c-Jun-N-terminal kinase (JNK) pathway.
MedLine Citation:
PMID:  20959642     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
c-Jun N-terminal kinase (JNK) pathway has been shown to be essential for cell cycle progression and mitosis. We previously showed that this pathway is activated in mitotic granulosa cells of follicles from transitional to antral stages. In this study, we, therefore, aimed to investigate whether this signaling pathway has any effect on in-vitro growth of murine preantral follicles and granulosa cell cycle control. Two structurally different pharmacologic JNK inhibitors, SP600125 and AS601245, were used in the experiments. First their inhibitory concentrations were determined in granulosa cells by Western blot analysis. Then preantral follicles isolated from immature and adult C57BL/6 mice were cultured in matrigel and standard culture plates for 6 days with these inhibitors. Spontaneously immortalized rat granulosa cells (SIGCs) were first synchronized at G1/S and G2/M stages of cell cycle and then treated with JNK inhibitors. Cell cycle progression was analyzed with Bromodeoxyuridine (BrdU) assay and flow cytometry analysis. Both inhibitors significantly inhibited phosphorylation of c-Jun in granulosa cells at 25, 50, and 100 μmol/L concentrations. Isolated preantral follicles cultured with these inhibitors exhibited arrested growth in culture in a dose-dependent manner. Cell cycle analyses showed that both inhibitors impair the progression of cell cycle at S phase and G2/M transition of granulosa cells. These results suggest that JNK pathway is essential for in vitro growth of preantral follicle growth and regulates both S phase and G2/M stages of cell cycle in granulosa cells.
Authors:
Ozgur Oktem; Erkan Buyuk; Kutluk Oktay
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-19
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  18     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-09     Completed Date:  2011-07-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  269-76     Citation Subset:  IM    
Affiliation:
Laboratory of Fertility Preservation and Molecular Reproduction, Departments of Obstetrics & Gynecology, Cell Biology & Anatomy, and Medicine, New York Medical College, Valhalla, New York 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetonitriles / pharmacology
Animals
Anthracenes / pharmacology
Benzothiazoles / pharmacology
Cell Cycle / drug effects,  physiology
Female
Granulosa Cells
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Mice
Mice, Inbred C57BL
Ovarian Follicle / drug effects,  enzymology*,  growth & development*
Phosphorylation / physiology
Protein Kinase Inhibitors / pharmacology
Signal Transduction / drug effects
Grant Support
ID/Acronym/Agency:
KO8 43339//PHS HHS; R01HD043339/HD/NICHD NIH HHS; R01HD053112/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/1,3-benzothiazol-2-yl(2-((2-(3-pyridinyl)ethyl)amino)-4-pyrimidinyl)acetonitrile; 0/Acetonitriles; 0/Anthracenes; 0/Benzothiazoles; 0/Protein Kinase Inhibitors; 0/anthra(1,9-cd)pyrazol-6(2H)-one; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

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