Friedman A, Weiss S, Levy N, Meidan R
Section of Immunology, Department of Animal Sciences, Faculty of Agricultural, Environmental and Food Sciences, Hebrew University of Jerusalem, Rehovot, Israel.
Biol Reprod. 2000 Dec;63(6):1905-12. doi: 10.1095/biolreprod63.6.1905.
The role of tumor necrosis factor alpha (TNF alpha) and its type I receptor (TNFRI) in structural luteolysis was investigated. A semiquatitative reverse-transcription polymerase chain reaction (RT-PCR) was used to characterize the pattern of TNFRI mRNA expression within the corpus luteum (CL) throughout the estrous cycle and its cellular distribution. Increase in TNFRI mRNA levels was recorded both in regressed luteal tissue and in CL of cows injected with prostaglandin F(2 alpha). All three major cell types composing the CL, steroidogenic (large and small) and endothelial cells expressed the TNFRI gene. A densitometric analysis of TNFRI mRNA expression revealed that resident endothelial cells had significantly higher levels of TNFRI mRNA than steroidogenic luteal cells. The physiological effects associated with TNFRI expression were investigated in the various luteal cell types. TNF alpha-induced programmed cell death (PCD) in dose- and time-dependent manners of cultured luteal endothelial cells (LECs) but not of in vitro luteinized steroidogenic cells. Several lines of evidence are provided to show that progesterone regulates luteal cell survival: 1) CL and LECs express progesterone receptor mRNA, 2) physiological levels of the steroid abolished TNF alpha-induced PCD of LECs, and 3) progesterone-producing cells are protected from PCD. In conclusion, this study suggests that TNF alpha-induced PCD during structural luteolysis is mediated by TNFRI, primarily affects endothelial cells, and that the decline in progesterone, preceding structural luteolysis, is a prerequisite for the initiation of apoptosis in endothelial cells.
研究了肿瘤坏死因子α（TNFα）及其I型受体（TNFRI）在结构性黄体溶解中的作用。采用半定量逆转录聚合酶链反应（RT-PCR）来表征整个发情周期中黄体（CL）内TNFRI mRNA的表达模式及其细胞分布。在退化的黄体组织以及注射前列腺素F（2α）的奶牛的CL中均记录到TNFRI mRNA水平升高。构成CL的所有三种主要细胞类型，即类固醇生成细胞（大细胞和小细胞）和内皮细胞均表达TNFRI基因。对TNFRI mRNA表达的光密度分析显示，驻留内皮细胞的TNFRI mRNA水平明显高于类固醇生成黄体细胞。在各种黄体细胞类型中研究了与TNFRI表达相关的生理效应。TNFα以剂量和时间依赖性方式诱导培养的黄体内皮细胞（LEC）发生程序性细胞死亡（PCD），但对体外黄体化的类固醇生成细胞无此作用。提供了几条证据表明孕酮调节黄体细胞存活：1）CL和LEC表达孕酮受体mRNA，2）该类固醇的生理水平消除了TNFα诱导的LEC的PCD，3）产生孕酮的细胞免受PCD影响。总之，本研究表明，TNFα在结构性黄体溶解过程中诱导的PCD由TNFRI介导，主要影响内皮细胞，并且在结构性黄体溶解之前孕酮的下降是内皮细胞凋亡启动的先决条件。
