Molecular mechanism ofapoptosis in target organs of sex steroid hormones

1.我们观察了阉割对小鼠精囊和附睾上皮细胞凋亡的影响，发现如下。(1)从出生到成年，阉割诱导这些器官的上皮细胞凋亡。(2)这些器官在缓慢生长阶段的凋亡程度低于随后的快速生长阶段。通过对Fas或Fas配体缺失突变小鼠的实验，我们发现Fas- Fas配体系统在小鼠精囊、附睾、前列腺和凝结腺的去势诱导的细胞凋亡中几乎没有作用。我们发现雌激素剥夺后小鼠子宫上皮细胞凋亡与线粒体细胞色素C向细胞质的释放、caspase-3的激活、Bak或Bax/Bcl-2或Bcl-xL的比例以及线粒体电压依赖性阴离子通道（VDAC）的数量有关。这些结果表明：(1)线粒体在雌激素剥夺诱导的子宫上皮细胞凋亡中起重要作用。(2)凋亡过程受Bcl-2家族蛋白调控。(3) VDAC的增加增强了细胞对凋亡的敏感性，因为VDAC被认为是细胞色素C从线粒体转移到细胞质的通道。

1.We examined the effect of castration on apoptosis in the epithelia of the mouse seminal vesicle and epididymis, and found the followings. (1) Castration induces apoptosis in the epithelia of these organs from birth to adulthood. (2) The extent of apoptosis is lower at the slowly growing stage of these organs than at their rapidly growing stage thereafter.2.By the experiments with mutant mice deficient in Fas or Fas ligand, we have shown that the Fas- Fas ligand system plays little role in castration-induced apoptosis in the mouse seminal vesicle, epididymis, prostate and coagulating gland.3.We have shown that apoptosis in the mouse uterine epithelium after estrogen deprivation correlates to release of cytochrome C in mitochondria into cytoplasm, activation of caspase-3, the ratio of Bak or Bax/Bcl-2 or Bcl-xL and the amount of voltage dependent anion channel (VDAC) in the mitochondria. These results suggest the followings. (1) Mitochondria play an important role in estrogen deprivation-induced apoptosis in the uterine epithelium. (2) This apoptotic process is regulated by proteins of the Bcl-2 family. (3) The increase in VDAC enhances the sensitivity of cells to apoptosis since VDAC is thought to be a channel, through which cytochrome C moves from mitochondria to cytoplasm.