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Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434
Author(s) -
Verga Falzacappa Cecilia,
Mangialardo Claudia,
Patriarca Valentina,
Bucci Barbara,
Amendola Donatella,
Raffa Salvatore,
Torrisi Maria Rosaria,
Silvestrini Giuliana,
Ballanti Paola,
Moriggi Giulia,
Stigliano Antonio,
Brunetti Ercole,
Toscano Vincenzo,
Misiti Silvia
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21849
Subject(s) - hormone , biology , apoptosis , cell cycle , thyroid , medicine , thyroid hormone receptor , endocrinology , cell growth , flow cytometry , receptor , microbiology and biotechnology , biochemistry , genetics
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. J. Cell. Physiol. 221: 242–253, 2009. © 2009 Wiley‐Liss, Inc