Molecular endocrinological study on the local regulatory mechanism of the proliferation, differentiation and apoptosis of female reproductive cells

评价了生长因子如甲状腺激素、IGF-I、EGF、TGF β和TNF α作为颗粒细胞增殖、分化和凋亡过程调节剂的潜力。甲状腺激素、胰岛素、IGF-I和EGF被发现在培养的颗粒细胞中作为FSH作用的上调剂，而TGF β和TNF α被证明在细胞中作为FSH作用的下调剂。DNA 3 '-末端标记法显示FSH、IGF-I和FGF抑制颗粒细胞凋亡DNA片段化，而TGF β和TNF α刺激颗粒细胞凋亡DNA片段化。这表明主要暴露于卵泡存活因子如FSH、IGF-I和EGF可能是选择生长卵泡的原因，而主要暴露于致闭锁因子如TGF β和TNF α可能是卵泡闭锁的原因。颗粒细胞是已知生长最快的正常细胞类型之一。实际上，c-myc mRNA在欠成熟卵泡的颗粒细胞中大量表达。c-myc在未成熟卵泡颗粒细胞中的表达具有阶段特异性，提示c-myc参与了未成熟卵泡的自主生长。erb-A在小卵泡颗粒细胞中的表达也比在大卵泡颗粒细胞中的表达更丰富。因此，这些癌基因的表达，无论是单独或组合，可能在卵泡发育早期的自主颗粒细胞增殖中发挥作用。此外，在最近的证据的基础上，Fas抗原介导的凋亡信号，Fas抗原在退化的黄体和闭锁的卵泡中的大量表达表明Fas抗原通过凋亡过程参与黄体退化和卵泡闭锁。

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.