Role of nitric oxide in implantation and menstruation
Role of nitric oxide in implantation and menstruation
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DOI：
10.1093/humrep/15.suppl_3.96
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发表时间：
2000-08-01
影响因子：
6.1
通讯作者：
Garfield, RE
中科院分区：
文献类型：
--
作者：
Chwalisz, K;Garfield, RE
一氧化氮（NO）是多种生物过程的主要旁分泌介质，包括血管功能和炎症。在血管中，NO由低输入组成型内皮NO合酶（eNOS）产生，并且是有效的血管扩张剂和血小板聚集抑制剂。诱导型NOS同工型（iNOS）能够产生高浓度的NO，其具有促炎特性。子宫内膜NOS表达的免疫组织化学和分子生物学研究以及NOS抑制剂的动物实验表明，NO在子宫内膜容受性、着床和月经等子宫内膜功能中起重要作用。在啮齿类动物中，iNOS和eNOS在着床部位高度上调，NOS抑制剂与抗孕激素在抑制妊娠建立方面显示出协同作用。在人子宫内膜中，eNOS主要在黄体期定位于腺上皮和子宫内膜微血管内皮。在月经期间的子宫内膜上皮、免疫活性子宫内膜细胞和蜕膜化基质细胞中发现了iNOS。在灵长类动物中，NO可能通过诱导组织破裂和血管舒张以及通过抑制血小板聚集而参与月经出血的开始和维持。子宫内膜来源的NO也可能在月经期间子宫肌层松弛中发挥作用。这些研究为NO供体和抑制剂在子宫疾病中的应用开辟了新途径。NO供体可用于治疗痛经和促进生育。抗孕激素、孕激素受体调节剂和iNOS抑制剂可用于治疗和预防异常子宫出血。
Nitric oxide (NO) is a major paracrine mediator of various biological processes, including vascular functions and inflammation. In blood vessels, NO is produced by the low-input constitutive endothelial NO synthase (eNOS) and is a potent vasodilator and platelet aggregation inhibitor. The inducible NOS isoform (iNOS) is capable of producing NO at high concentrations which have pro-inflammatory properties. Immunohistochemical and molecular studies of endometrial NOS expression, as well as animal experiments with NOS inhibitors, indicate that NO plays an important role in endometrial functions such as endometrial receptivity, implantation and menstruation. In rodents, both iNOS and eNOS are highly up-regulated in the implantation sites, and NOS inhibitors show synergistic effects with antiprogestins in inhibiting the establishment of pregnancy. In the human endometrium, eNOS have been localized in the glandular epithelium and in endometrial microvascular endothelium, primarily during the luteal phase. iNOS has been found in the endometrial epithelium during menstruation, in immunocompetent endometrial cells, and in decidualized stromal cells. In primates, NO may be involved in the initiation and maintenance of menstrual bleeding by inducing tissue breakdown and vascular relaxation as well as by inhibiting platelet aggregation. Endometrium-derived NO may also play a role in myometrial relaxation during menstruation. These studies open up new applications for NO-donating and-inhibiting agents in uterine disorders. NO donors may be useful in the treatment of dysmenorrhoea and for promoting fertility. Antiprogestins, progesterone receptor modulators and iNOS inhibitors may find applications in the treatment and prevention of abnormal uterine bleeding.