Mitogenic action, regulation, and localization of insulin-like growth factors in the human fetal adrenal gland.
Mitogenic action, regulation, and localization of insulin-like growth factors in the human fetal adrenal gland.
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DOI：
10.1210/jcem.76.4.8473412
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发表时间：
1993-04
期刊：
影响因子：
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通讯作者：
S. Mesiano;S. Mellon;R. Jaffe
中科院分区：
文献类型：
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作者：
S. Mesiano;S. Mellon;R. Jaffe
多肽生长因子可能通过介导ACTH的趋性作用，在调节人胎儿肾上腺皮质生长中发挥重要作用。编码胰岛素样生长因子-II(IGF-II)的mRNA在人胎儿肾上腺中含量很高，并且在培养的胎儿肾上腺皮质细胞中受ACTH刺激。因此，我们在原代培养的人胎儿肾上腺皮质细胞和整个人胎儿肾上腺中，研究了IGF-II和一种密切相关的多肽IGF-I的促分裂作用、调节和定位。重组人胰岛素样生长因子-I和胰岛素样生长因子-II以剂量依赖的方式刺激胎儿肾上腺皮质细胞的增殖(1-1,000 ng/mL；0.133-133nM)。当浓度为1000 ng/m L(133 NM)时，两种多肽的细胞数均增加1.8-2倍。IGF-I或IGF-II(100 ng/m L；13.3 nM)与碱性成纤维细胞生长因子(bFGF；0.1 ng/m L；6 pm)或表皮生长因子(EGF；1.0 ng/m L；0.17 nM)联合使用时，对细胞增殖的影响比单独使用bFGF、EGF或两者中的任一种都要大，提示两者之间存在相加作用。用原位杂交方法检测培养的肾上腺皮质细胞中IGF-II基因的表达，并用ACTH刺激其丰度。相反，在培养的胎带细胞中未检测到IGF-I mRNA，且不受ACTH的调节。在整个人胎儿肾上腺中，IGF-II mRNA在终止区、胎儿区和包膜中均可检测到，而IGF-I mRNA仅在包膜中检测到，而在两个皮质区中未检测到。Northern印迹分析发现，编码IGF-II的mRNA在胎儿肾上腺(16-22周)中含量很高，在成人肾上腺中几乎检测不到，而编码IGF-I的mRNA在胎儿肾上腺中含量很低，但在成人肾上腺中含量很高。由于IGF-II在人胎儿肾上腺皮质中高表达，并受ACTH的调节，我们认为它是调节人胎儿肾上腺生长的两种IGF中的主导因子。胰岛素样生长因子-II与碱性成纤维细胞生长因子、表皮生长因子的协同促分裂作用以及ACTH对其表达的调节，支持了IGF-II可能与碱性成纤维细胞生长因子、可能的表皮生长因子共同参与调节中期人胎儿肾上腺皮质快速生长的假说。
Polypeptide growth factors may play an important role in the regulation of human fetal adrenal cortical growth by mediating the tropic actions of ACTH. The abundance of mRNA encoding insulin-like growth factor-II (IGF-II) is high in the human fetal adrenal gland and is stimulated by ACTH in cultured fetal adrenal cortical cells. Therefore, we studied the mitogenic action, regulation, and localization of IGF-II and a closely related peptide, IGF-I, in primary cultures of human fetal adrenal cortical cells and whole human fetal adrenal glands. Recombinant human IGF-I and IGF-II stimulated proliferation of fetal adrenal cortical cells in a dose-dependent fashion (1-1000 ng/mL; 0.133-133 nM). At 1000 ng/mL (133 nM), both peptides increased cell number 1.8- to 2-fold. Combinations of IGF-I or -II (100 ng/mL; 13.3 nM) with basic fibroblast growth factor (bFGF; 0.1 ng/mL; 6 pM) or epidermal growth factor (EGF; 1.0 ng/mL; 0.17 nM) had a greater effect on proliferation than bFGF, EGF, or either of the IGFs alone, suggesting an additive interaction. IGF-II mRNA was detected in cultured adrenal cortical cells by in situ hybridization analysis, and its abundance was stimulated by ACTH. In contrast, IGF-I mRNA was not detected in cultured fetal zone cells and was not regulated by ACTH. In whole human fetal adrenal glands, IGF-II mRNA was detected in the definitive and fetal zones and in the capsule, whereas IGF-I mRNA was detected only in the capsule and not in the two cortical zones. Using Northern blot analysis, we found that mRNA encoding IGF-II was present in high abundance in fetal adrenal glands (16-22 weeks) and barely detectable in adult adrenals, whereas mRNA encoding IGF-I was present in very low abundance in the fetal adrenal, but was high in adult human adrenals. As IGF-II expression is high in the human fetal adrenal cortex and is regulated by ACTH, we propose that it is the dominant of the two IGFs regulating human fetal adrenal growth. The cooperative mitogenic effect of IGF-II with bFGF and EGF and the regulation of its expression by ACTH support the hypothesis that IGF-II may act as a mediator, in concert with bFGF and possibly EGF, of the tropic action of ACTH in regulating the rapid growth of the human fetal adrenal cortex during midgestation.