Hwang J J, Macinga D, Rorke E A
Department of Environmental Health Science and Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
J Clin Endocrinol Metab. 1996 Sep;81(9):3379-84. doi: 10.1210/jcem.81.9.8784100.
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 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 [3H]g-lycocyamine incorporation in human cervical stromal cell cultures. These results indicate the relaxin may regulate cervical ripening in humans, as it does in other species, by direct effects on cervical cells.
在怀孕期间，子宫颈在大小和硬度方面会发生显著变化，这些变化旨在促进正常分娩。这些变化受多种激素因素的控制。实验和临床研究表明，一种蛋白质激素——松弛素，在促进宫颈软化中发挥作用。松弛素对子宫颈产生作用的一个可能靶点是基质。在本文报道的研究中，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有何直接影响。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，但被发现可调节与细胞外基质重塑相关的基质细胞活性。当使用明胶底物凝胶时，松弛素刺激了几种宫颈基质蛋白酶活性的分泌，包括36 kDa、52 kDa和116 kDa的蛋白酶。使用乙二胺四乙酸、1,10 - 菲咯啉和L - 半胱氨酸进行的抑制剂研究确定这些明胶酶为金属蛋白酶。雌二醇和孕酮均未增强松弛素的作用。当用传统的胶原纤维测定法测量时，观察到松弛素诱导胶原酶活性呈浓度依赖性增加。最后，如在人宫颈基质细胞培养物中通过[³H] - 甘氨酰胺掺入所示，发现松弛素可增加糖胺聚糖的合成。这些结果表明，松弛素可能像在其他物种中一样，通过对宫颈细胞的直接作用来调节人类的宫颈成熟。
