Document Detail

Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434.
MedLine Citation:
PMID:  19562675     Owner:  NLM     Status:  MEDLINE    
Numerous evidences indicate that thyroid hormones exert an important role in the regulation of the reproductive system in the adult female. Although a clear demonstration of the thyroid-ovarian interaction is still lacking, it is conceivable that thyroid hormones might have a direct role in ovarian physiology via receptors in granulosa cells. In this study we analyzed if thyroid hormone treatment could affect cell proliferation and survival of COV434 cells. To this aim cell growth experiments and cell cycle analyses by flow cytometry were performed. Secondly the T(3) survival action was tested by TUNEL assay and MD30 cleavage analysis. We showed that T(3), and not T(4), can protect ovarian granulosa cells COV434 from apoptosis, regulating cell cycle and growth in the same cells. The increase in cell growth resulted in an augmented percentage of the cells in the S phase and, in a reduction of the doubling time (18%). Subsequently apoptotic pathway induced by serum deprivation has been evaluated in the cells exposed or not to thyroid hormone treatment. The T(3) treatment was able to remarkably counteract the apoptotic process. Even at the ultrastructural level there was an evident protective effect of T(3) in the cells that, besides the maintenance of the original morphology and, the absence of basophilic cytoplasm, conserved normal junctional areas. Furthermore, the protective T(3) effect evaluated by FACS analysis in the presence of a PI3K inhibitor revealed, as also confirmed by Western Blot on pAkt, that the PI3K pathway is crucial in T(3) survival action.
Cecilia Verga Falzacappa; Claudia Mangialardo; Valentina Patriarca; Barbara Bucci; Donatella Amendola; Salvatore Raffa; Maria Rosaria Torrisi; Giuliana Silvestrini; Paola Ballanti; Giulia Moriggi; Antonio Stigliano; Ercole Brunetti; Vincenzo Toscano; Silvia Misiti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  221     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-07-29     Completed Date:  2009-08-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-53     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Wiley-Liss, Inc.
II Faculty of Medicine, Sapienza, University of Rome, Rome, Italy.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism
Apoptosis / drug effects
Caspase 9 / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Shape / drug effects
Cell Survival / drug effects
Cytoprotection / drug effects
Granulosa Cells / cytology*,  drug effects*,  enzymology,  ultrastructure
Keratin-18 / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Thyroxine / pharmacology*
Triiodothyronine / pharmacology*
Reg. No./Substance:
0/Keratin-18; 6893-02-3/Triiodothyronine; 7488-70-2/Thyroxine; EC 3-Kinase; EC Proteins c-akt; EC 3.4.22.-/Caspase 9

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