Department of Medicine and Rheumatology, and Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Endocrine. 2013 Apr;43(2):387-93. doi: 10.1007/s12020-012-9766-0. Epub 2012 Aug 17.
Lactation is an important event in all-mammalian species. To investigate the role of pregnancy-associated plasma protein (PAPP)-A in lactogenesis, we determined (i) PAPP-A expression in mouse mammary glands and (ii) the biological functions of PAPP-A in mammary epithelial cells. PAPP-A mRNA level was low during early mid pregnancy and increased during mid-late pregnancy, and then slightly decreased during lactation. Cell proliferation signals, but not differentiation, increased PAPP-A mRNA expression in HC11 mammary epithelial cells. Treatment of recombinant PAPP-A protein stimulated HC11 cell proliferation and suppressed the expression of β-casein mRNA, which is one of the milk proteins and cell differentiation marker. Surprisingly, in forcing expression experiment, PAPP-A increased β-casein mRNA expression. Our data suggest that PAPP-A has different roles on intracellular expressing and extracellular treatment to mammary epithelial cells. Taken together, in early pregnancy, circulating PAPP-A protein might be supplied from other organs and stimulates mammary gland growth. In contrast, during mid-late pregnancy, local PAPP-A expression begins and enhances cell differentiation within mammary epithelial cell.
哺乳是所有哺乳动物物种中的一个重要事件。为了研究妊娠相关血浆蛋白（PAPP-A）在泌乳中的作用，我们确定了（i）PAPP-A 在小鼠乳腺中的表达，以及（ii）PAPP-A 在乳腺上皮细胞中的生物学功能。在妊娠中期早期，PAPP-A mRNA 水平较低，在妊娠中期晚期增加，然后在哺乳期略有下降。细胞增殖信号而非分化信号增加了 HC11 乳腺上皮细胞中 PAPP-A mRNA 的表达。重组 PAPP-A 蛋白处理刺激 HC11 细胞增殖并抑制乳蛋白和细胞分化标志物之一β-酪蛋白 mRNA 的表达。令人惊讶的是，在强制表达实验中，PAPP-A 增加了β-酪蛋白 mRNA 的表达。我们的数据表明，PAPP-A 对乳腺上皮细胞的细胞内表达和细胞外处理有不同的作用。总之，在妊娠早期，循环中的 PAPP-A 蛋白可能来自其他器官，并刺激乳腺生长。相比之下，在妊娠中期晚期，局部 PAPP-A 的表达开始，并增强乳腺上皮细胞内的细胞分化。
