Role of Parathyroid Hormone-Related Protein on Mammary Gland

牛奶中含有多种激素和细胞因子。然而，关于乳腺机制的确切信息仍不清楚。甲状旁腺激素相关蛋白（PTHrP）由泌乳乳腺产生，以生物活性形式存在于乳汁中。本研究通过体外三维培养牛乳腺细胞，探讨表皮生长因子（EGF）、转化生长因子(TGF)- β和脂多糖（LPS）对甲状旁腺激素相关蛋白分泌的影响。从奶牛产犊后1-6周的泌乳乳腺中分离出乳腺腺泡病毒。新鲜或冷冻保存的乳腺腺泡在胶原凝胶中培养，在胶原包被的培养插入物或塑料盘子上培养。用n端放射免疫法测定PTHrP的产生。用northern分析法检测培养的牛乳腺细胞中PTHrP mRNA的表达。此外，用A375细胞生长抑制实验和7TD1杂杂瘤增殖实验分别测定了白细胞介素(IL)-1和IL-6的产生。EGF和tgf - β处理后，培养液中PTHrP的产生和PTHrP mRNA的表达呈剂量依赖性增加。LPS对PTHrP的产生无显著影响，但对IL-1和IL-6的产生有剂量依赖性。这些数据表明，泌乳奶牛的乳腺细胞是可以体外培养的，并且可以调节分泌PTHrP。这些结果也提示EGF和tgf - β可能是调控乳腺PTHrP分泌的重要因素。PTHrP的生理生理作用尚不确定。位于乳腺泡底部的肌上皮细胞对乳腺泡的收缩起作用。PTHrP可能在调节乳汁或乳汁成分进入肺泡腔中发挥作用。因此，该体外模型将有助于研究泌乳乳腺中PTHrP的功能及其调控。少

Various hormones and cytokines are present in milk. However, precise information on the mechanism in the mammary gland is still unclear. Parathyroid hormone-related protein (PTHrP) is produced by the lactating mammary gland and is present in milk in a biologically active form. This investigation was performed to determine the effect of epidermal growth factor (EGF), transforming growth factor (TGF)-beta, and lipopolysaccharide (LPS) on parathyroid hormone-related protein secretion by three dimensional culture of bovine mammary cells in vitro. Mammary acini were isolated from lactating mammary glands of cows at 1-6 weeks after calving. Fresh or cryopreserved mammary acini were cultured within collagen gels and on collagen coated culture inserts or plastic dishes. PTHrP production was measured by N-terminal radioimmunoassay. PTHrP mRNA expression from cultured bovine mammary cells was determined by northern analysis. Moreover, production of interleukin (IL)-1 and IL-6 were measured using … More a A375 cell growth inhibiton assay and a 7TD1 hybridoma proliferation assay, respectively. PTHrP production in the culture medium as well as PTHrP mRNA expression was increased by treatment with EGF and TGF-beta in dose dependent manner. There is no significant effect of LPS on PTHrP production, but LPS increased both IL-1 and IL-6 productions in dose dependent manner. These data demonstrated that the mammary cell from lactating cows could be cultured in vitro and secreted PTHrP in a regulated manner. These results also indicate that EGF and TGF-beta may be important factors in the regulation of PTHrP secretion in the mammary gland. The pthophysiological role of PTHrP is uncertain. Myoepithelial cells situated in the basal position of mammary alveoli act on the alveolar contraction. PTHrP could play a role in the regulation of milk or milk components into the alveolar lumen. In conclusion, this in vitro model will be useful to investigate the function and regulation of PTHrP in the lactating mammary gland. Less