Shandong Key Laboratory of Animal Bioengineering and Disease Prevention, College of Animal Science and Technology, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China.
Sci Rep. 2017 Jul 14;7(1):5479. doi: 10.1038/s41598-017-06054-w.
The MEN1 gene, which encodes the protein Menin, was investigated for its regulatory role in milk protein synthesis in mammary glands. Menin responds to nutrient and hormone levels via the PI3K/Akt/mTOR pathway. Bovine mammary epithelial cells and tissues were used as experimental models in this study. The results revealed that the milk protein synthesis capacity of mammary epithelial cells could be regulated by MEN1/Menin. The overexpression of Menin caused significant suppression of factors involved in the mTOR pathway, as well as milk protein κ-casein (CSNK). In contrast, a significant increase in these factors and CSNK was observed upon MEN1/Menin knockdown. The repression of MEN1/Menin on the mTOR pathway was also observed in mammary gland tissues. Additionally, MEN1/Menin was found to elicit a negative response on prolactin (PRL) and/or insulin (INS), which caused a similar downstream impact on mTOR pathway factors and milk proteins. Collectively, our data indicate that MEN1/Menin could play a regulatory role in milk protein synthesis through mTOR signaling in the mammary gland by mediating the effects of hormones and nutrient status. The discovery of Menin's role in mammary glands suggests Menin could be potential new target for the improvement of milk performance and adjustment of lactation period of dairy cows.
MEN1 基因编码 Menin 蛋白，该基因在乳腺中参与调控乳蛋白合成。Menin 通过 PI3K/Akt/mTOR 通路对营养和激素水平做出响应。本研究以奶牛乳腺上皮细胞和组织为实验模型。结果表明，MEN1/Menin 可调节乳腺上皮细胞的乳蛋白合成能力。Menin 过表达显著抑制 mTOR 通路相关因子和乳蛋白κ-酪蛋白（CSNK）。相反，敲低 MEN1/Menin 后，这些因子和 CSNK 的表达显著增加。在乳腺组织中也观察到 MEN1/Menin 对 mTOR 通路的抑制作用。此外，还发现 MEN1/Menin 对催乳素（PRL）和/或胰岛素（INS）产生负反馈，这对 mTOR 通路因子和乳蛋白产生类似的下游影响。综上所述，我们的数据表明，MEN1/Menin 可通过调节激素和营养状态的影响，通过 mTOR 信号通路在乳腺中调节乳蛋白合成。Menin 在乳腺中的作用的发现表明，Menin 可能成为提高奶牛产奶性能和调整泌乳期的新的潜在靶标。
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