Progestagenic effects of tibolone are target gene-specific in human endometrial cells.
Progestagenic effects of tibolone are target gene-specific in human endometrial cells.
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替勃龙的孕激素作用在人类子宫内膜细胞中具有靶基因特异性。
DOI：
10.1016/j.jsgi.2006.05.004
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Tseng,Linda
中科院分区：
文献类型：
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作者：
Zhang,Wei;Mazella,James;Kloosterboer,HeleniusJ;Tseng,Linda
目的：Tibolone （Tib）除了具有组织特异性雌激素活性外，还具有孕激素活性。本研究的目的是利用已知在人子宫内膜腺细胞和基质细胞中受孕激素调节的靶基因来确定Tib及其代谢物的孕激素作用。方法：从子宫内膜组织碎片中分离人子宫内膜腺细胞和基质细胞，分别与Tib及其代谢物孵育。采用实时聚合酶链反应（Real-time polymerase chain reaction， PCR）检测子宫内膜腺细胞中17β羟基类固醇脱氢酶（17βHSD, type 2）和硫代转移酶（SULT1E1） mRNA含量，以及子宫内膜基质细胞中泌乳素（PRL）和胰岛素样生长因子结合蛋白-1 (IGFBP1) mRNA含量。结果：在腺细胞中，Tib和Δ4-tibolone （Δ4Tib）显著增加了17βHSD和SULT1E1 mRNA的含量。在基质细胞中，Tib和Δ4Tib增加了PRL mRNA（与黄体酮相比增加了约30%的能力），对IGFBP1 mRNA的影响很小。抗黄体酮RU486逆转了黄体酮或Tib对SULT1E1和PRL的诱导。另外，2种3羟基羟溴酮代谢物，特别是3β ohtib，也有一定的孕激素作用。结论：数据显示，Tib和Δ4Tib通过诱导17βHSD和SULT1E1对子宫内膜腺细胞有明显的孕激素作用，而在基质细胞中对PRL的诱导作用较弱，对IGFBP1的影响较小。此外，3βOHTib代谢物表达孕激素活性。这两种细胞的不同作用可能有利于维持子宫内膜细胞处于静止状态。
Objectives:Tibolone (Tib) exhibits progestagenic activities in addition to its tissue-specific estrogenic activities. The purpose of the current study was to determine the progestagenic actions of Tib and its metabolites using target genes known to be regulated by progestins in human endometrial glandular and stromal cells.Methods:Human endometrial glandular and stromal cells were isolated from endometrial tissue fragments and separately incubated with Tib and its metabolites. Real-time polymerase chain reaction (PCR) was used to determine the mRNA content of 17βhydroxy steroid dehydrogenase (17βHSD, type 2) and sulfotransferase (SULT1E1) in endometrial glandular cells, and prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP1) in endometrial stromal cells.Results:In glandular cells, Tib and Δ4-tibolone (Δ4Tib) significantly increased the content of 17βHSD and SULT1E1 mRNA. In stromal cells, Tib and Δ4Tib increased PRL mRNA (∼ 30% of the capacity compared to progesterone) and had little effect on IGFBP1 mRNA. Anti-progestin, RU486, reversed the induction of SULT1E1 and PRL by progesterone or Tib. Also, the two 3 hydroxyl tobolone metabolites, especially 3βOHTib, showed some progestagenic effects.Conclusions:The data showed that Tib and Δ4Tib exhibited clear progestagenic effects in endometrial glandular cells by inducing 17βHSD and SULT1E1, while in stromal cells the response was weaker in the induction of PRL and had little effect on IGFBP1. In addition, the 3βOHTib metabolite expressed progestagenic activity. These disparate effects in two types of cells may be beneficial for maintaining endometrial cells in a quiescent state.