Targeted disruption of LH receptor gene revealed the importance of uterine LH signaling.
Targeted disruption of LH receptor gene revealed the importance of uterine LH signaling.
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LH 受体基因的靶向破坏揭示了子宫 LH 信号传导的重要性。
DOI：
10.1016/j.mce.2004.09.011
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Rao,ChV
中科院分区：
文献类型：
--
作者：
Lin,DX;Lei,ZM;Li,X;Rao,ChV
以往的大量研究表明，LH 和 hCG 可以直接调节多种子宫功能。我们在本研究中调查了 LH 受体敲除动物的子宫表型是否也是由于子宫中缺乏 LH 的直接作用所致。表型包括子宫生长明显减少、子宫内膜和肌层厚度、子宫内膜腺体数量、管腔上皮高度和血管间隙减少。通过小鼠基因组 U74Av2 Affymetrix 基因芯片对子宫基因表达进行的分析显示，无效型动物和野生型动物之间 155 个基因的表达差异超过 3 倍（范围 3-53 倍）。其中，在无效动物的子宫中，89 个基因减少，66 个基因增加。半定量RT-PCR证实了几个选定基因的差异表达。减少的基因可分为18个功能家族，增加的基因可分为15个功能家族。半定量 RT-PCR、Western blotting 和免疫细胞化学表明，与野生型同胞相比，无效动物子宫中 ERβ、PR-A、PR-B 和 AR 的表达降低。二十一天的雌二醇和黄体酮替代疗法并没有使子宫内膜腺体数量的减少和一些表达减少或增加的基因正常化。治疗的部分成功表明，可能需要直接 LH 作用才能使子宫完全正常化。总之，敲除模型的研究结果再次证实，LH 和 hCG 通过增加卵巢合成类固醇激素直接或间接控制子宫功能，并且这两种作用都是正常子宫生物学所必需的。
Numerous previous studies have demonstrated that LH and hCG can directly regulate several uterine functions. We investigated in the present study, whether uterine phenotype in LH receptor knockout animals resulted also from the absence of direct actions of LH in the uterus. The phenotype consisted of marked growth reduction of uterus, decreased thickness of endometrial and myometrial layers, number of endometrial glands, height of luminal epithelium and vascular space. Analysis of uterine gene expression by mouse genome U74Av2 Affymetrix genechips revealed a differential expression of 155 genes by more than 3-fold (range 3–53-fold) between null and wild-type animals. Of these, 89 genes decreased and 66 increased in uterus of null animals. Semi-quantitative RT-PCR confirmed the differential expression of several selected genes. The decreased genes can be clustered into 18 functional families and the increased into 15 functional families. Semi-quantitative RT-PCR, Western blotting and immunocytochemistry demonstrated a decreased expression of ERβ, PR-A, PR-B and AR in uterus of null animals as compared with wild-type siblings. Twenty-one-day estradiol and progesterone replacement therapy did not normalize the decrease in the number of endometrial glands and several genes that either decreased or increased in expression. The partial success of therapy suggests that direct LH actions could be required to completely normalize the uterus. In summary, findings on the knockout model reaffirm that LH and hCG control uterine functions directly as well as indirectly through increasing ovarian synthesis of steroid hormones and both actions are required for normal uterine biology.