Expression of gelatinase B by trophoblast cells: Down-regulation by progesterone
Expression of gelatinase B by trophoblast cells: Down-regulation by progesterone
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DOI：
10.1016/s0002-9378(98)70420-x
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发表时间：
1998-03-01
影响因子：
9.8
通讯作者：
Yagel, S
中科院分区：
文献类型：
--
作者：
Shimonovitz, S;Hurwitz, A;Yagel, S
目的：明胶酶B（92 kd IV型胶原酶）参与胚泡着床和滋养层浸润。然而，很少有人知道这种酶在母胎界面的调节。已证明Progestrin可抑制子宫内膜细胞、子宫肌层和宫颈成纤维细胞分泌明胶酶B。有趣的是，明胶酶B的启动子包含一个孕酮反应元件，这可能解释孕酮对这种金属蛋白酶的转录激活。可以假设，孕酮分泌的滋养层细胞，代表胎儿的一部分fetomaternal接口，可能有一个作用，在调节明胶酶分泌和囊胚implantation.Study设计：为此，使用了孕早期滋养层细胞获得的孕早期妊娠终止。采用胰蛋白酶降解法和Percoll梯度离心法分离滋养层细胞。金属蛋白酶活性测定酶谱法，明胶酶B信使核糖核酸的表达被确定的解决方案杂交/核糖核酸酶保护assay.Results：原代细胞培养的滋养层细胞从怀孕的前三个月组成阐述了两个物种的IV型胶原酶（明胶酶A和B）作为评估明胶基质。孕酮处理以剂量依赖性方式减少明胶酶B种类的积累，给予孕酮受体拮抗剂奥那司酮（ZK-98.299）以剂量依赖性方式中和孕酮对明胶酶B的抑制作用，从而支持孕酮作用是受体介导的假设。孕酮可显著抑制滋养层细胞明胶酶B的表达，ZK-98.299可中和孕酮的抑制作用。结论：孕酮参与了滋养层细胞明胶酶B的调节。它可能是一个重要的调节明胶酶生产的母胎界面。
OBJECTIVE: It is now accepted that gelatinase B (92 kd type IV collagenase) is involved in blastocyst implantation and trophoblast invasion. However, little is known about the regulation of this enzyme at the fetomaternal interface. Progesterone has been demonstrated to inhibit gelatinase B secretion from endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the promotor of gelatinase B contains a progesterone-responsive element that may explain transcriptional activation of this metalloproteinase by progesterone. It may be hypothesized that progesterone secreted from trophoblast cells, representing the fetal part of the fetomaternal interface, may have a role in the regulation of gelatinase secretion and blastocyst implantation.STUDY DESIGN: To this end, use was made of first-trimester trophoblast cells obtained from first-trimester pregnancy terminations. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients. Metalloproteinase activity was measured by zymography, and the expression of the gelatinase B messenger ribonucleic acid was determined by the solution hybridization/ribonuclease protection assay.RESULTS: Primary cell cultures of trophoblasts from first trimesters of pregnancy constitutively elaborated two species of type IV collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with progesterone decreased the accumulation of a gelatinase B species in a dose-dependent fashion, Administration of a progesterone receptor antagonist onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the gelatinase B in a dose-dependent fashion, thus supporting the presumption that the progesterone effect is receptor mediated. Progesterone significantly attenuated the expression of gelatinase B by trophoblast cells, an effect that was neutralized by ZK-98.299.CONCLUSION: These observations provide strong indirect support for the participation of progesterone in the regulation of gelatinase B in trophoblast cells. It may be an important regulator of gelatinase production at the fetomaternal interface.