Huynh H
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, 169610, Singapore.
Growth Horm IGF Res. 2000 Feb;10(1):20-7. doi: 10.1054/ghir.2000.0137.
Involution of the uterus induced by oestrogen depletion is associated with a decrease in uterine insulin-like growth factor (IGF)-I and an increase in IGF binding protein (IGFBP) gene expression. We examined the effects of IGF-I on primary uterine myometrial cell proliferation, and on IGFBP-3 and IGFBP-4 gene expression. IGF-I enhanced DNA synthesis in these cells. In conditioned media, IGF-I increased IGFBP-3 accumulation by release of cell associated IGFBP-3. A low dose of IGF-I increased IGFBP-4 accumulation, and a high dose caused IGFBP-4 to disappear. In cell-free conditioned media IGF-I protected IGFBP-3 and enhanced IGFBP-4 proteolysis. Co-incubation of [(125)I]-IGFBP-4 with cell-free conditioned media cleaved IGFBP-4 into 18 and 12 kDa fragments. Northern blot analysis indicated that IGF-I increased IGFBP-4 mRNA accumulation by stabilizing the mRNA while IGFBP-3 gene expression was slightly decreased. The results demonstrate that IGF-I regulates IGFBP-4 post-trancriptionally and post-translationally, whereas IGFBP-3 is only affected post-translationally. By enhancing IGFBP-4 proteolysis, increasing cell-associated IGFBP-3 and stabilizing IGFBP-3, IGF-I may initiate a mitogenic response.
雌激素耗竭诱导的子宫 involution 与子宫胰岛素样生长因子（IGF）-I 的减少以及 IGF 结合蛋白（IGFBP）基因表达的增加有关。我们研究了 IGF-I 对原代子宫肌层细胞增殖以及对 IGFBP-3 和 IGFBP-4 基因表达的影响。IGF-I 增强了这些细胞中的 DNA 合成。在条件培养基中，IGF-I 通过释放细胞相关的 IGFBP-3 增加了 IGFBP-3 的积累。低剂量的 IGF-I 增加了 IGFBP-4 的积累，而高剂量则导致 IGFBP-4 消失。在无细胞条件培养基中，IGF-I 保护了 IGFBP-3 并增强了 IGFBP-4 的蛋白水解作用。[(125)I]-IGFBP-4 与无细胞条件培养基共同孵育将 IGFBP-4 切割成 18 和 12 kDa 的片段。Northern 印迹分析表明，IGF-I 通过稳定 mRNA 增加了 IGFBP-4 mRNA 的积累，而 IGFBP-3 基因表达略有下降。结果表明，IGF-I 在转录后和翻译后调节 IGFBP-4，而 IGFBP-3 仅在翻译后受到影响。通过增强 IGFBP-4 的蛋白水解作用、增加细胞相关的 IGFBP-3 以及稳定 IGFBP-3，IGF-I 可能引发有丝分裂反应。 （注：involution 此处可能是“退化”等意思，因未结合完整医学背景较难准确翻译）
