| Research Abstract |
The roles of growth factors, such as thyroid hormone, IGF-I,EGF,TGF beta and TNF alpha were evaluated for their potential as regulators of granulosa cell proliferation, differentiation and apoptotic process. Thyroid hormone, insulin, IGF-I and EGF were found to act as up-regulators of FSH actions in cultured granulosa cells, whereas TGF beta and TNF alpha were shown to act as down-regulators of FSH actions in the cells. The use of DNA 3'-end labeling method revealed that FSH,IGF-I and FGF suppressed apoptotic DNA fragmentation of granulosa cells, whereas TGF beta and TNF alpha stimulated apoptotic DNA fragmentation of the cells. This suggests that dominant exposure to follicle survival factors such as FSH,IGF-I,and EGF may be responsible for the selection of growing follicles, while dominant exposure to atretogenic factors such as TGF beta and TNF alpha may be responsible for follicle atresia. The granulosa cell is one of the most rapidly growing normal cell types known. Actually, c-myc mRNA was expressed abundantly in the granulosa cells of less-mature follicles. The stage-specific expression of the c-myc in immature granulosa cells may suggest c-myc participation in the autonomous growth of immature follicles. erb-A was also expressed more abundantly in small-follicle granulosa cells than in large-follicle granulosa cells. Thus, the expression of these oncogenes, either alone or in combination, may play a role in the autonomous granulosa cell proliferation early in follicular development. Furthermore, on the basis of the recent evidence, that the Fas antigen mediates an apoptotic signal, abundant expression of the Fas antigen in the regressing corpora lutea and atretic follicles suggests that the Fas antigen participates in luteal regression and follicular atresia through the apoptotic process.
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