Transforming growth factor B1 stimulated DNA synthesis in the granulosa cells of preantral follicles: negative interaction with epidermal growth factor

Biology of Reproduction
Peixin Yang, Shyamal K Roy

Abstract

EGF or TGFB1 alone stimulates but together attenuate granulosa cell DNA synthesis. Intact preantral follicles from hamsters were cultured with TGFB1, EGF, or both to reveal the mechanisms of such unique regulation. Follicular CCND2 (also known as cyclin D2), CDKN1B (also known as p27(kip1)), and the involvement of appropriate signaling intermediaries and kinases were examined. TGFB1, acting via SMAD2 and SMAD3, antagonized the degradation of CCND2 protein by blocking its phosphorylation. In contrast, TGFB1 supported CDKN1B degradation by involving MAPK14 (also known as p38 Map Kinase) and PKC, resulting in CDK4 activation and DNA synthesis. EGF via MAPK3/1 maintained functional levels of CCND2 through CCND2 synthesis as well as degradation. EGF and TGFB1 together inhibited CDK4 activation and DNA synthesis. EGF attenuated TGFB1 stimulated phosphorylation of SMAD3, TGFB1-induced activation of MAPK14 and PKC, and TGFB1 suppression of CCND2 degradation. In contrast, TGFB1 suppressed EGF-induced increase in CCND2 mRNA levels. The final outcome was CCND2 degradation without replenishment and decreased activities of MAPK14 and PKC leading to suppression of CDK4 activation. The results indicate that each growth factor involves a separ...Continue Reading

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Citations

Apr 9, 2011·Reproduction : the Official Journal of the Society for the Study of Fertility·Karen L ReaderJennifer L Juengel
May 22, 2013·Reproduction : the Official Journal of the Society for the Study of Fertility·Yexia LiJian Xu
Apr 28, 2018·Reproductive Biology and Endocrinology : RB&E·Virginie MaillardSebastien Elis
Apr 16, 2009·American Journal of Physiology. Endocrinology and Metabolism·Qing HuangPeter C K Leung

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Methods Mentioned

BETA
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