Role of IGF-I in normal mammary development
Role of IGF-I in normal mammary development
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DOI：
10.1023/a:1005998832636
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发表时间：
1998-02-01
影响因子：
3.8
通讯作者：
Kleinberg, DL
中科院分区：
文献类型：
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作者：
Kleinberg, DL
生长激素(GH)现在被认为是负责乳腺导管形态发生的垂体因素。乳房发育在青春期是由于生长激素和雌激素在末端芽(TEB)的形成上的协同作用。TEBS延伸到乳腺脂肪垫的物质中，导致导管的形态发生。最终，整个乳房脂肪垫容纳了一个复杂的导管网络。IGF-I或DES(1-3)IGF-I模拟生长激素对去垂体、去性腺大鼠TEB形成的作用。由于GH协同刺激乳腺内的IGF-I mRNA，我们假设IGF-I部分介导了GH在乳腺发育中的作用。在过量表达IGF-I、DES(1-3)IGF-I或IGFBP-3的转基因小鼠中的研究表明，IGF-I导致哺乳期小鼠乳腺肥大，并防止哺乳期后乳腺退化。GH或IGF-I在乳腺癌发生中的潜在作用，以及动物研究对人类的适用性进行了讨论。
Growth hormone (GH) is now believed to be the pituitary factor that is responsible for mammary ductal morphogenesis. Mammary development at puberty occurs because of synergy between GH and estrogen on formation of terminal end buds (TEBs). TEBs extend into the substance of the mammary gland fat pad, resulting in ductal morphogenesis. Ultimately, the whole mammary fat pad accommodates a complex network of ducts. IGF-I or des(1-3) IGF-I mimic the actions of GH on TEB formation in hypophysectomized, gonadectomized rats. Since GH stimulates IGF-I mRNA within the mammary gland synergistically, we hypothesize that IGF-I partially mediates actions of GH in mammary gland development.Studies in transgenic mice overexpressing IGF-I, des(1-3) IGF-I, or IGFBP-3 show that IGF-I causes ductal hypertrophy in the lactating mouse and prevention of post-lactational mammary gland involution. One of the mechanisms for this effect involves apoptosis.The potential role of GH or IGF-I in mammary carcinogenesis, and the applicability of animal studies to humans, are discussed.