Mechanism underlying the regulation of apoptosis in female reproductive cells

女性生殖细胞凋亡调控机制

基本信息

批准号：
10470346
负责人：
MARUO Takeshi
金额：
$ 5.95万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

1) Sex steroidal regulation of leiomyoma growth and apoptosis.Progesterone up-regulates the PCNA protein expression in cultured leiomyoma cells. Consistently, the PCNA labeling index in leiomyoma tissues predominated in the secretory, progesterone-dominated, phase of the menstrual cycle, compared to that in the proliferative phase. Furthermore, we demonstrated that EGF-like protein expression in cultured leiomyoma cells was up-regulated by progesterone, whereas EGF receptor expression in those cells was up-regulated by 17β-estradiol. We have also demostrated a greater abundance of Bcl-2 protein in leiomyomas, relative to the normal myometrium of the same individual uterus, and that Bcl-2 protein expression in leiomyoma cells predominated in the secretory, progesterone-dominated phase of the menstrual cycle, compared to that in the proliferative phase. The abundant expression of Bcl-2 protein in leiomyoma may be one of the molecular bases for the enhanced growth of leiomyoma, relative t … More o that of normal myometrium, in the uterus.2) Granulosa cell proliferation and apoptosis during follicular growth and regressionWe examined the proliferative activity of granulosa cells during follicular growth and regression on the basis of PCNA expression. The PCNA expression was augmented by FSH in a dose-dependent manner. FSH, IGF-I and EGF acted as up-regulators of the proliferative activty of granulosa cells, whereas TNFα and TGFβ acted as down-regulators of granulosa cell proliferation. Analysis of DNA 3'-end labeling and Fas antigen and its ligand expression in the ovary suggested that apoptosis in atretic primordial and preantral follicles first occurred in the oocyte, whereas apoptosis in atretic antral follicles first occurred in the granulosa cells. Futhermore, we noted that FSH and IGF-I inhibited apoptosis of granulosa cells, whereas TGFβ and TNFα stimulated apoptosis of the cells. These results suggest 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 TGFβ and TNFα may be responsible for follicle atresia. Less

1）性类固醇对平滑肌瘤生长和细胞凋亡的调节。预抑制在培养的平滑肌瘤细胞中上调PCNA蛋白表达。一致地，与增殖阶段相比，平滑肌瘤组织中的PCNA标记指数在月经周期的秘密，以孕激素为主的相比为主导。此外，我们证明了培养的平滑肌瘤细胞中EGF样蛋白的表达被孕酮上调，而这些细胞中的EGF受体表达被17β-雌二醇上调。与同一单个子宫的正常肌层相比，我们还显示了平滑肌瘤中Bcl-2蛋白的丰度，并且与在增殖阶段相比，在男性心周期的秘密，孕酮占主导阶段的bcl-2蛋白表达中，bcl-2蛋白的表达占了。 Bcl-2蛋白在平滑肌瘤中的丰富表达可能是增强平滑肌瘤生长的分子碱基之一，相对……更多的o肌层肌层，在子宫中。 FSH以剂量依赖性方式增强了PCNA的表达。 FSH，IGF-I和EGF充当颗粒细胞增殖活性的上调，而TNFα和TGFβ充当颗粒细胞增殖的下调节剂。 DNA 3'-末端标记和FAS抗原的分析及其在卵巢中的配体表达表明，卵母细胞中首次发生肌膜原始和蛋白质卵泡的凋亡，而植物肛门卵泡的凋亡首先发生在granulosa细胞中。 futhermore，我们注意到FSH和IGF-I抑制了颗粒细胞的凋亡，而TGFβ和TNFα刺激了细胞的凋亡。这些结果表明，诸如FSH，IGF-I和EGF之类的叶片生存因子的主要暴露可能是造成生长卵泡的选择，而显性暴露于TGFβ和TNFα等促源性因子可能是folicle folicle antreesia的原因。较少的