Overexpression of des(1-3) insulin-like growth factor 1 in the mammary glands of transgenic mice delays the loss of milk production with prolonged lactation
Overexpression of des(1-3) insulin-like growth factor 1 in the mammary glands of transgenic mice delays the loss of milk production with prolonged lactation
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DOI：
10.1095/biolreprod.105.043992
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Fiorotto, ML
中科院分区：
文献类型：
--
作者：
Hadsell, DL;Torres, DT;Fiorotto, ML
在长时间的哺乳期间，乳腺逐渐丧失产奶的能力。在农业物种中，可以通过施用外源生长激素 (GH) 来减缓这种下降，据信外源生长激素是通过胰岛素样生长因子 1 (IGF1) 发挥作用的。我们之前的工作证明了 des(1-3)IGF1 过表达转基因小鼠 (Tg[Wap-des{1-3}IGF1]8266 Jmr)（以下简称 WAP-DES 小鼠）的自然乳腺退化延迟。本研究测试了过度表达 des(1-3)IGF1 会延迟长时间哺乳期间产奶量损失的假设。因此，我们通过持续同窝交叉寄养人为延长泌乳时间来检查 WAP-DES 小鼠的泌乳性能。随着时间的推移，WAP-DES 和对照小鼠的泌乳能力和乳腺发育均下降。然而，WAP-DES 小鼠的下降速度要慢 40%。在延长哺乳期间，两组的乳腺细胞凋亡增加了 3 倍，但基因型之间没有差异。 WAP-DES 小鼠中小鼠 IGF1 的血浆浓度降低，而转基因人 IGF1 的血浆浓度在长时间哺乳期间升高。 WAP-DES 小鼠中乳腺 IGF1 受体的磷酸化增加，但仅限于长时间哺乳期间。非转基因小鼠的血浆催乳素随着哺乳时间的延长而降低，但 WAP-DES 小鼠的血浆催乳素仍然很高。 WAP-DES 小鼠在长时间哺乳期间保持较高的体重和较大的去脂体重。这些数据支持这样的结论：过度表达的 des(13)IGF1 通过局部和直接激活乳腺 IGF1 受体以及通过对催乳素分泌和可能的营养平衡的全身影响，增强了长时间哺乳期间的乳汁合成和乳腺发育。
During prolonged lactation, the mammary gland gradually loses the capacity to produce milk. In agricultural species, this decline can be slowed by administration of exogenous growth hormone (GH), which is believed to act through insulin-like growth factor 1 (IGF1). Our previous work demonstrated delayed natural mammary gland involution in des(1-3)IGF1-overexpressing transgenic mice (Tg[Wap-des{1-3}IGF1]8266 Jmr), hereafter referred to as WAP-DES mice. The present study tested the hypothesis that overexpressed des(1-3)IGF1 would delay the loss of milk production during prolonged lactation. Accordingly, we examined lactational performance in WAP-DES mice by artificially prolonging lactation with continual litter cross-fostering. Over time, lactational capacity and mammary development declined in both WAP-DES and control mice. However, the rate of decline was 40% slower in WAP-DES mice. Mammary cell apoptosis increased by 3-fold in both groups during prolonged lactation but was not different between genotypes. Plasma concentrations of murine IGF1 were decreased in WAP-DES mice, while those of the transgenic human IGF1 were elevated during prolonged lactation. Phosphorylation of the mammary IGF1 receptor was increased in the WAP-DES mice, but only during prolonged lactation. Plasma prolactin decreased with prolonged lactation in nontransgenic mice but remained high in WAP-DES mice. The WAP-DES mice maintained a higher body mass and a greater lean body mass during prolonged lactation. These data support the conclusion that overexpressed des(13)IGF1 enhanced milk synthesis and mammary development during prolonged lactation through localized and direct activation of the mammary gland IGF1 receptor and through systemic effects on prolactin secretion and possibly nutrient balance.