Bogorad R L, Ostroukhova T Y, Orlova A N, Rubtsov P M, Smirnova O V
Laboratory of Endocrinology, Faculty of Biology, Lomonosov Moscow State University, Vorob'ev Hills, 119992, Moscow, Russian Federation.
J Endocrinol. 2006 Feb;188(2):345-54. doi: 10.1677/joe.1.06468.
Prolactin participates in the regulation of liver function. However, prolactin receptor (PrlR) expression and its regulation have been described only for hepatocytes. In this study, we investigated the expression and regulation of PrlR isoforms in the other important intrahepatic cellular compartment: the biliary epithelial cells, or cholangiocytes. Our aim was to determine whether prolactin should be considered as a potential regulator of cholangiocyte function under normal and pathological conditions. Cholangiocytes and hepatocytes were differentially isolated from rat liver. PrlR expression was analysed at the mRNA level by isoform-specific semiquantitative PCR, and at the protein level by immunostaining of liver sections. Hormonal regulation of PrlR expression was evaluated by comparing intact rats with gonadectomized, pituitary-grafted or bromocriptine-treated animals. Common bile-duct ligation was used as the experimental model of cholestasis. Our results demonstrate that the expression pattern and regulation of PrlR isoforms is totally different in cholangiocytes compared with hepatocytes: (1) mature rat cholangiocytes express low levels of PrlR, while it is very high in hepatocytes, (2) only the long isoform is detected in cholangiocytes, while the short isoform predominates in hepatocytes and (3) PrlR levels in cholangiocytes are induced by obstructive cholestasis, but not by sex hormones or prolactin, while it is the opposite in hepatocytes. From these data, the actions of prolactin on liver are anticipated to exhibit strong cell-type specificity in both normal and pathological conditions.
催乳素参与肝脏功能的调节。然而，催乳素受体（PrlR）的表达及其调控仅在肝细胞中得到描述。在本研究中，我们调查了PrlR亚型在另一个重要的肝内细胞区室：胆管上皮细胞（即胆管细胞）中的表达和调控。我们的目的是确定在正常和病理条件下，催乳素是否应被视为胆管细胞功能的潜在调节因子。从大鼠肝脏中分别分离出胆管细胞和肝细胞。通过亚型特异性半定量PCR在mRNA水平分析PrlR表达，通过肝脏切片免疫染色在蛋白质水平分析PrlR表达。通过比较完整大鼠与去性腺、垂体移植或溴隐亭处理的动物来评估PrlR表达的激素调节。胆总管结扎用作胆汁淤积的实验模型。我们的结果表明，与肝细胞相比，胆管细胞中PrlR亚型的表达模式和调控完全不同：（1）成熟大鼠胆管细胞中PrlR表达水平较低，而肝细胞中PrlR表达水平非常高；（2）胆管细胞中仅检测到长亚型，而肝细胞中短亚型占主导；（3）胆管细胞中的PrlR水平由梗阻性胆汁淤积诱导，而非由性激素或催乳素诱导，而肝细胞中的情况则相反。根据这些数据，预计催乳素在正常和病理条件下对肝脏的作用均表现出强烈的细胞类型特异性。
