Alternative pathways of ovarian apoptosis: death for life
Alternative pathways of ovarian apoptosis: death for life
复制标题
DOI：
10.1016/s0006-2952(03)00485-4
复制
发表时间：
2003-10-15
影响因子：
5.8
通讯作者：
Hirsh, L
中科院分区：
文献类型：
--
作者：
Amsterdam, A;Sasson, R;Hirsh, L
卵巢细胞死亡是维持人类和其他哺乳动物卵巢功能稳态的重要过程。它确保了优势卵泡的选择和多余卵泡的死亡。反过来，这一过程最大限度地减少了怀孕期间多个胚胎发育的可能性，并确保少数但健康的胚胎发育。在每个发情/月经周期中，通过程序性细胞死亡使旧黄体退化对于维持卵巢类固醇生成的正常周期性至关重要。虽然有多种途径可以决定细胞的死亡或存活，但内分泌、旁分泌和自分泌因子之间，以及原癌基因、肿瘤抑制基因、存活基因和死亡基因之间的串扰在决定卵巢体细胞和生殖细胞的命运中起着重要作用。永生化大鼠和人类类固醇颗粒细胞系的建立和原代颗粒细胞纯群体的调查允许控制类固醇生成和颗粒细胞凋亡的机制进行系统研究。我们已经发现，在颗粒细胞凋亡的初始阶段，孕酮的产生并没有减少。相反。我们发现，在全部细胞崩溃之前，它在由饥饿、cAMP、p53或肿瘤坏死因子7刺激施加的凋亡刺激开始后升高达24小时。这些观察结果提出了另一种独特的凋亡途径的可能性，这种途径不涉及与线粒体结构和类固醇生成功能破坏相关的线粒体细胞色素C释放。使用来自凋亡细胞的mRNA和Affyssin DNA微阵列，我们发现颗粒酶B（一种通常存在于免疫系统的细胞毒性T淋巴细胞和自然杀伤细胞中的蛋白酶）在颗粒细胞中表达和活化。从而允许凋亡信号绕过线粒体信号进行凋亡，这可以保持它们的类固醇生成活性直到完全的细胞破坏。这种独特的细胞凋亡途径确保了雌/月经周期中雌二醇和孕酮释放的周期性，即使在细胞凋亡的初始阶段。(C)2003年爱思唯尔公司All rights reserved.
Ovarian cell death is an essential process for the homeostasis of ovarian function in human and other mammalian species. It ensures the selection of the dominant follicle and the demise of excess follicles. In turn, this process minimizes the possibility of multiple embryo development during pregnancy and assures the development of few, but healthy embryos. Degeneration of the old corpora lutea in each estrus/menstrual cycle by programmed cell death is essential for maintaining the normal cyclicity of ovarian steroidogenesis. Although there are multiple pathways that can determine cell death or survival, crosstalk among endocrine, paracrine and autocrine factors, as well as among protooncogenes, tumor suppressor genes, survival genes and death genes, play an important role in determining the fate of ovarian somatic and germ cells. The establishment of immortalized rat and human steroidogenic granulosa cell lines and the investigation of pure populations of primary granulosa cells allows for systematic studies of the mechanisms that control steroidogenesis and apoptosis of granulosa cells. We have discovered that during initial stages of granulosa cell apoptosis progesterone production does not decrease. In contrast. we found that it is elevated for up to 24 hr following the onset of the apoptotic stimuli exerted by starvation, cAMP, p53 or tumor necrosis factor 7 stimulation, before total cell collapse. These observations raise the possibility for an alternative unique apoptotic pathway, one that does not involve mitochondrial cytochrome C release associated with the destruction of mitochondrial structure and steroidogenic function. Using mRNA from apoptotic cells and Affymetrix DNA microarray we discovered that Granzyme B, a protease that normally resides in T cytotoxic lymphocytes and natural killer cells of the immune system is expressed and activated in granulosa cells. thereby allowing the apoptotic signals to bypass mitochondrial signals for apoptosis, which can preserve their steroidogenic activity until complete cell destruction. This unique apoptotic pathway assures the cyclicity of estradiol and progesterone release in the estrus/menstrus cycle even during the initial stage of apoptosis. (C) 2003 Elsevier Inc. All rights reserved.