Relaxin modulates human cervical stromal cell activity

Relaxin modulates human cervical stromal cell activity
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DOI:
10.1210/jc.81.9.3379
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发表时间:
1996-09-01
影响因子:
5.8
通讯作者:
Rorke, EA
Rorke, EA
中科院分区:
医学2区
文献类型:
--
作者:
Hwang, JJ;Macinga, D;Rorke, EA

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子宫颈在怀孕期间经历了大小和一致性的深刻变化,旨在促进正常分娩。这些变化是由多种激素因素控制的。实验和临床研究表明,松弛素是一种蛋白质激素,在促进宫颈软化中起作用。松弛素对子宫颈作用的一个可能的靶点是间质。在这里报道的研究中,使用正常人宫颈基质细胞培养物来确定松弛素对宫颈细胞的直接影响。浓度范围为0.10-100 ng/mL的松弛素对人宫颈基质细胞增殖没有影响,但发现其调节与细胞外基质重塑相关的基质细胞活性。当使用明胶基质凝胶时,松弛素刺激几种宫颈基质蛋白酶活性的分泌,包括36、52和116 kDa。使用乙二胺四乙酸、1,10-菲咯啉和L-半胱氨酸的抑制剂研究将这些明胶酶鉴定为金属蛋白酶。雌二醇和孕酮都不能增强松弛素的作用。松弛素诱导的浓度依赖性增加胶原酶活性时,观察到与传统的胶原纤维测定。最后,松弛素被发现增加糖胺聚糖的合成,如在人宫颈基质细胞培养物中的[H-3]甘氨胞苷掺入所示。这些结果表明,松弛素可以调节宫颈成熟在人类,因为它在其他物种,通过对宫颈细胞的直接影响。
The cervix undergoes profound changes in size and consistency during pregnancy which are designed to facilitate a normal delivery. These changes are under the control of a number of hormonal factors. Experimental and clinical studies suggest that relaxin, a protein hormone, plays a role in promoting cervical softening. One possible target site for the effects of relaxin on the cervix is the stroma. In the studies reported here, cultures of normal human cervical stromal cells were used to determine what direct effects relaxin has on cervical cells. Relaxin at concentrations ranging from 0.10-100 ng/mL had no effect on human cervical stromal cell proliferation, but was found to modulate stromal cell activity related to the remodeling of extracellular matrix. When gelatin substrate gels were used, relaxin stimulated the secretion of several cervical stromal proteinase activities, including 36, 52, and 116 kDa. Inhibitor studies using ethylenediamine tetraacetate, 1,10-phenanthroline, and L-cysteine identify these gelatinases as metalloproteinases. Neither estradiol nor progesterone augmented the effects of relaxin. A relaxin-induced concentration-dependent increase in collagenase activity was observed when measured with a conventional collagen fibril assay. Finally, relaxin was found to increase glycosaminoglycan synthesis, as indicated by [H-3]glycocyamine incorporation in human cervical stromal cell cultures. These results indicate that relaxin may regulate cervical ripening in humans, as it does in other species, by direct effects on cervical cells.