Matrix metalloproteinases in normal menstruation

Matrix metalloproteinases in normal menstruation
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DOI:
10.1093/humrep/11.suppl_2.124
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发表时间:
1996-10-01
期刊:
影响因子:
6.1
通讯作者:
Woolley, DE
Woolley, DE
中科院分区:
医学1区
文献类型:
--
作者:
Salamonsen, LA;Woolley, DE

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基质金属蛋白酶(MMPs)与月经密切相关,尽管其组织抑制因子TIMP-1和TIMP-2的信使RNA存在于月经周期中,但只有在月经周期周围和月经周期的子宫内膜中才能检测到原MMP1和MMP3的信使RNA,免疫组织化学证明MMP1、TIMP-3和TIMP-9与月经内膜的降解组织特异性相关,活化的肥大细胞和嗜酸性粒细胞释放MMPs表达的调节因子和潜伏酶的激活物,也是月经内膜的显著特征。培养的子宫内膜间质细胞释放基质金属蛋白酶-1、-2、-3、-9和金属基质金属蛋白酶-1和-2,而上皮细胞产生的基质金属蛋白酶-1和-2很少,从间质细胞培养中撤出孕酮(10天培养的最后4天)增加了所有四种酶的释放:除基质细胞外的所有酶都被白介素1或肿瘤坏死因子α刺激。我们推测,改变基质细胞及其抑制物的平衡和激活基质金属蛋白酶是月经时组织降解的先决条件。这是由上皮细胞、基质细胞、肥大细胞和嗜酸性粒细胞的黄体酮撤退和旁分泌因子共同调节的。
Matrix metalloproteinases (MMP) are strongly implicated in menstruation, Messenger RNA for proMMP-1 and -3 was detectable in normal cycle endometrium only peri-menstrually and menstrually, although mRNA for their tissue inhibitors, TIMP-1 and TIMP-2, was present throughout the cycle, MMP-1, -3 and -9 were demonstrated immunohistochemically to be specifically associated with degraded tissue in menstrual endometrium, Activated mast cells and eosinophils, which release regulators of MMP expression and activators of latent enzymes, were also a marked feature of menstrual endometrium. Cultured endometrial stromal cells released MMP-1, -2, -3 and -9 and TIMP-1 and -2, whereas production by epithelial cells was minimal, Progesterone withdrawal from stromal cell cultures (for the final 4 days of a 10 day culture) increased the release of all four enzymes: all but MMP-2 were also stimulated by interleukin-1 or tumour necrosis factor alpha added to short-term stromal cultures, We postulate that an alteration in the balance of MMP and their inhibitors and the activation of MMP are prerequisites for tissue degradation at menstruation, and that this is regulated by a combination of progesterone withdrawal and paracrine factors from epithelial and stromal cells and from mast cells and eosinophils.