IR@PKUHSC  > 北京大学第三临床医学院
学科主题妇产科学
芳香化酶与多囊卵巢综合征子宫内膜增生的关系及来曲唑对其影响
赵磐琳
2009-11-25
导师乔杰
专业妇产科学
授予单位北京大学
授予地点北京大学第三临床医学院
学位博士
关键词多囊卵巢综合征 子宫内膜增生 芳香化酶 来曲唑
其他题名The relationship of aromatase P450 and endometrial hyperplasia in polycystic ovary sydrome and the effect of letrozole on endometrium cells
分类号R711.75
摘要

目的:研究多囊卵巢综合征患者子宫内膜局部芳香化酶的表达特点,并初步探讨多囊卵巢综合征患者子宫内膜异常增殖的可能机制及治疗靶点。

方法:利用免疫组织化学技术,检测多囊卵巢综合征患者及对照组子宫内膜中芳香化酶的表达特点;利用实时定量RT-PCR方法,比较多囊卵巢综合征患者及对照组子宫内膜中芳香化酶mRNA的表达水平;体外培养子宫内膜腺上皮及间质细胞,给予不同浓度的睾酮及来曲唑刺激,测定培养液中雌二醇含量变化,以实时定量RT-PCR方法检测细胞芳香化酶mRNA表达变化,并以流式细胞术检测细胞增殖状态。

结果:芳香化酶在对照组子宫内膜中呈低表达,在腺上皮细胞主要定位于细胞膜、细胞核及细胞浆,而在间质细胞,则主要表达在细胞膜及细胞浆。与对照组相比,多囊卵巢综合征患者的子宫内膜中,芳香化酶mRNA表达水平明显增高。在子宫内膜细胞的体外培养体系中,10-6M睾酮处理细胞后,培养液中雌二醇含量明显增加;而培养液中加入10-7M睾酮已经引起子宫内膜细胞中芳香化酶mRNA表达量的明显增高。当在培养液中进一步加入来曲唑后发现,10-5M浓度时即能明显抑制雌二醇的生成,同时细胞芳香化酶的mRNA的表达水平明显降低。经流式细胞术分析发现,10-6M、10-7M睾酮干预下,子宫内膜细胞中G2期、S期细胞比率未见明显增加,但10-5M来曲唑可使其比率下降。

结论:(1)人子宫内膜细胞中有芳香化酶的表达;(2)PCOS患者子宫内膜局部芳香化酶的表达增高;(3)睾酮可引起体外培养的子宫内膜细胞中芳香化酶合成增加、雌二醇生成量增加,但未见明显促细胞增殖作用;(4)来曲唑可以抑制体外培养的子宫内膜细胞中芳香化酶的表达及雌二醇的生成,并可能对细胞的异常增殖有抑制作用。

英文摘要

Objective: To study the expression of aromatase P450 in the endometrium of polycystic ovary syndrome patients and that in the control group. To discuss the possible mechanism and the target point of treatment to the endometrial hyperplasia in the polycystic ovary syndrome.

Methods: Immunohistochemical method was used to observe the expression of aromatase P450 in the endometrium of polycystic ovary sydrome patients and that of control. Semiquantitative analysis in the aromatase P450 expression of mRNA and protein level had been done with real-time quantitative RT-PCR method. After the endometrium cell were stimulated by testosterone and Letrozole in vitro, the estradiol  level was determined, the expression of cell aromatase P450 mRNA was measured and cell proliferation was detected by flow cytometry machine.

Results: Low expression of aromatase P450 was found in cell membrane, nucleus and cytoplasmic of glandular epithelium cells and membrane and cytoplasma of stromal cells in normal endometrium. The aromatase P450 mRNA level increased in endometrium of polycystic ovary sydrome patients comparing with control. When the endometrium cells were cultured with 10-6M testosterone, the estradiol level in culture medium increased. When the endometrium cells were cultured with 10-7M testosterone, the expression of aromatase P450 mRNA in endometrium cell significantly increased. An inhibitory effect on estradiol generation and expression of  aromatase P450 mRNA was observed when the endometrium cell were treated with 10-5M Letrozole. Flow cytometry ananlysis showed that there was an decrease in the ratio of G2 and S-phase cells of endometrium epithilial cells treated with 10-5M letrozole, but no significantly change was seen when the cells treated with 10-7M  or 10-6M testosterone.

Conclusions: We can detect the expression of aromatase P450 in the endometium. There is an increased expression of aromatase P450 in polycystic ovary sydrome patients endometrium. Androgen stimulation enhance the synthesis of aromatase P450 mRNA and the production of estrdial of endometrium cells in vitro, but cannot promote the cell growth. Letrozole can restrain the expression of aromatase P450 mRNA and the production of estrdial while inhibit cell proliferation.

语种中文
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文献类型学位论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/124743
专题北京大学第三临床医学院
作者单位北京大学第三临床医学院
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赵磐琳. 芳香化酶与多囊卵巢综合征子宫内膜增生的关系及来曲唑对其影响[D]. 北京大学第三临床医学院. 北京大学,2009.
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