Mechanism underlying the regulation of apoptosis in female reproductive cells

1)性甾体激素对子宫肌瘤生长和凋亡的调节孕激素上调培养子宫肌瘤细胞PCNA蛋白表达。子宫肌瘤组织中PCNA标记指数在月经周期中以分泌期为主，而在增殖期则以孕酮为主。此外，我们还证实了EGF样蛋白在培养的平滑肌瘤细胞中的表达被孕酮上调，而EGF受体在这些细胞中的表达被17β-雌二醇上调。我们还证明了一个更大的丰度Bcl-2蛋白在平滑肌瘤，相对于正常的子宫肌层的同一个人的子宫，和Bcl-2蛋白表达在平滑肌瘤细胞占主导地位的分泌期，甾体为主的月经周期相比较，在增殖期。Bcl-2蛋白在子宫肌瘤中的高表达可能是子宫肌瘤生长速度加快的分子基础之一，与子宫肌瘤的恶性程度有关。 ...更多信息 2）卵泡生长和消退过程中颗粒细胞的增殖和凋亡我们在PCNA表达的基础上检测了卵泡生长和消退过程中颗粒细胞的增殖活性。FSH可促进PCNA表达，且呈剂量依赖性。FSH、IGF-I和EGF对颗粒细胞增殖活性起上调作用，而TNFα和TGFβ对颗粒细胞增殖活性起下调作用。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，而闭锁腔卵泡的凋亡首先发生在颗粒细胞中。FSH和IGF-I抑制颗粒细胞凋亡，而TGFβ和TNFα刺激颗粒细胞凋亡。这些结果表明，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TGFβ和TNFα可能是导致卵泡闭锁的原因。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