Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I
Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I
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DOI：
10.1210/en.2003-1112
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发表时间：
2004-07-01
期刊：
影响因子：
4.8
通讯作者：
Diaugustine, RP
中科院分区：
文献类型：
--
作者：
Richards, RG;Klotz, DM;Diaugustine, RP
小鼠乳腺的发育发生在出生后。局部生长因子途径的激素激活刺激通过脂肪基质的未发育腺体的快速伸长和分支。早期的研究表明，GH是乳腺导管形态发生所必需的，IGF-I介导GH的这一作用。在本研究中，我们表明，成年IGF-I-m/m突变小鼠表现出显着降低乳腺和肝脏IGF 1转录水平与对照组相比。整个安装的成年IGF-I（m/m）乳腺显示导管延伸到脂肪垫的限制，然而，分叉分支点的突变体的导管树的数量减少了一半相比，野生型腺体。与此相反，成年突变小鼠肝脏特异性缺失的igf 1基因获得Cre/loxP重组策略保持正常水平的乳腺igf 1转录本，并没有表现出在这个器官的分支缺陷。据以前报道，这种特定的肝脏IGF-I损失导致血清IGF-I（内分泌）水平下降约75%，而组织IGF 1转录水平保持不变。基于这些发现，我们提出旁分泌，而不是内分泌，IGF-I是重要的乳腺分支形态发生。
The development of the mouse mammary gland occurs postnatally. Hormonal activation of local growth factor pathways stimulates rapid elongation and branching of the rudimentary gland through the fatty stroma. Earlier studies showed that GH is required for mammary gland ductal morphogenesis and that IGF-I mediates this action of GH. In the present study we show that adult IGF-I-m/m mutant mice exhibit a marked reduction in levels of mammary gland and liver igf1 transcripts compared with controls. Whole mounts of the adult IGF-I(m/m)mammary glands revealed ducts that extended to the limits of the fat pad; however, the number of bifurcation branch points in the ductal tree of the mutants was reduced by half compared with that of wild-type glands. In contrast, adult mutant mice with a liver-specific deletion of the igf1 gene obtained by Cre/loxP recombination strategy maintained the normal levels of mammary gland igf1 transcripts and did not exhibit a branching deficit in this organ. It was previously reported that this specific loss of liver IGF-I causes serum levels of IGF-I (endocrine) to decrease by approximately 75%, whereas the levels of tissue igf1 transcripts remain unchanged. On the basis of these findings, we propose that paracrine, not endocrine, IGF-I is important for mammary branching morphogenesis.