Mechanism underlying the regulation of apoptosis in female reproductive cells

1)性激素对子宫肌瘤生长和凋亡的调节。孕酮上调培养的子宫肌瘤细胞中增殖细胞核抗原的表达。与增生期相比，子宫肌瘤组织中的增殖细胞核抗原标记指数始终在月经周期的分泌期、孕酮占优势的阶段占优势。此外，我们还发现孕酮可上调子宫肌瘤细胞中表皮生长因子样蛋白的表达，而17β-雌二醇则可上调子宫肌瘤细胞中表皮生长因子受体的表达。我们还发现，与同一子宫的正常子宫肌层相比，子宫肌瘤中的Bcl2蛋白表达更为丰富，并且与增生期相比，Bcl2蛋白在月经周期以黄体酮为主的分泌期的肌瘤细胞中的表达占主导地位。Bcl2蛋白在子宫肌瘤中的丰富表达可能是促进肌瘤生长的分子基础之一，相对于…2)卵泡生长和消退过程中颗粒细胞的增殖和凋亡检测卵泡生长和消退过程中颗粒细胞的增殖活性。FSH以剂量依赖的方式增强增殖细胞核抗原的表达。促卵泡激素、胰岛素样生长因子-I和表皮生长因子上调颗粒细胞的增殖活性，而肿瘤坏死因子α和转化生长因子β下调颗粒细胞的增殖。DNA 3‘末端标记和Fas抗原及其配体在卵巢中的表达分析表明，闭锁的原始卵泡和腔前卵泡的凋亡首先发生在卵母细胞中，而闭锁的腔前卵泡的凋亡首先发生在颗粒细胞中。此外，促卵泡刺激素和胰岛素样生长因子-I抑制颗粒细胞的凋亡，而转化生长因子β和肿瘤坏死因子α促进颗粒细胞的凋亡。这些结果表明，卵泡存活因子如卵泡刺激素、胰岛素样生长因子和表皮生长因子的优势暴露可能与生长卵泡的选择有关，而转化生长因子β和肿瘤坏死因子α的优势暴露可能是卵泡闭锁的原因。较少

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