Prolactin-mediated regulation of lipid biosynthesis genes in vivo in the lactating mammary epithelial cell
Prolactin-mediated regulation of lipid biosynthesis genes in vivo in the lactating mammary epithelial cell
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DOI：
10.1152/ajpendo.00083.2011
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发表时间：
2011-06-01
影响因子：
5.1
通讯作者：
Anderson, Steven M.
中科院分区：
文献类型：
--
作者：
Rudolph, Michael C.;Russell, Tanya D.;Anderson, Steven M.
已知催乳素 (PRL) 在怀孕小鼠的乳腺泡增殖中发挥重要作用，但其在哺乳中的作用更难以确定。改变 PRL 受体及其下游信号分子表达的基因操作会导致发育缺陷，可能直接或间接影响分泌激活和泌乳。为了检查 PRL 在哺乳期的体内作用，在产后第二天，每 8 小时给哺乳小鼠注射溴隐亭 (BrCr)，导致血清 PRL 水平下降约 95%。尽管分泌性肺泡的形态变化很轻微，但 BrCr 8 小时后，幼仔的生长受到显着抑制。磷酸化 STAT5 在 4 小时内降至不可检测的水平。治疗 8 小时后观察到乳蛋白基因表达、β-酪蛋白和 α-乳清蛋白降低。为了评估对脂质合成基因的乳腺特异性影响，我们分离了耗尽乳腺脂肪细胞的乳腺上皮细胞（MEC）。仅经过 8 小时的 BrCr 处理，MEC 中涉及葡萄糖摄取、糖酵解、磷酸戊糖分流、脂肪酸从头合成和三酰甘油生物合成的基因表达就下降了 19 倍。经 BrCr 处理的小鼠腺体显示，细胞内细胞质脂滴减少了两倍，胞质 β-酪蛋白也减少了两倍。这些数据表明，PRL 信号调节 MEC 特异性脂肪生成基因表达，并且 PRL 信号协调小鼠哺乳期间的乳汁合成和乳腺上皮细胞存活。
Prolactin (PRL) is known to play an essential role in mammary alveolar proliferation in the pregnant mouse, but its role in lactation has been more difficult to define. Genetic manipulations that alter expression of the PRL receptor and its downstream signaling molecules resulted in developmental defects that may directly or indirectly impact secretory activation and lactation. To examine the in vivo role of PRL specifically in lactation, bromocriptine (BrCr) was administered every 8 h to lactating mice on the second day postpartum, resulting in an similar to 95% decrease in serum PRL levels. Although morphological changes in secretory alveoli were slight, by 8 h of BrCr, pup growth was inhibited significantly. Phosphorylated STAT5 fell to undetectable levels within 4 h. Decreased milk protein gene expression, beta-casein, and alpha-lactalbumin, was observed after 8 h of treatment. To assess mammary-specific effects on lipid synthesis genes, we isolated mammary epithelial cells (MECs) depleted of mammary adipocytes. Expression of genes involved in glucose uptake, glycolysis, pentose phosphate shunt, de novo synthesis of fatty acids, and biosynthesis of triacylglycerides was decreased up to 19-fold in MECs by just 8 h of BrCr treatment. Glands from BrCr-treated mice showed a twofold reduction in intracellular cytoplasmic lipid droplets and a reduction in cytosolic beta-casein. These data demonstrate that PRL signaling regulates MEC-specific lipogenic gene expression and that PRL signals coordinate the milk synthesis and mammary epithelial cell survival during lactation in the mouse.