Sorenson R L, Stout L E
Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis 55455, USA.
Endocrinology. 1995 Sep;136(9):4092-8. doi: 10.1210/endo.136.9.7649117.
Lactogenic hormones, PRL and placental lactogen, are important regulators of insulin secretion and islet beta-cell proliferation. In this study we examined the presence of PRL receptor immunoreactivity in pancreatic islets of Langerhans using PRL receptor monoclonal antibodies provided by Dr. Paul Kelly. Studies were performed using islets isolated from neonatal, adult, and day 14 pregnant rats. The islets were examined by immunohistochemistry and laser scanning confocal microscopy. In neonatal rat islets, PRL receptors were observed in beta- and alpha-cells, but not in delta-cells. Among islet beta- and alpha-cells there was heterogeneity of cellular staining for PRL receptors. A small portion of the cells was intensely stained for PRL receptors. However, the majority of the cells had a much lower level of staining intensity, suggesting that most islet cells have a low level of PRL receptors. In general, alpha-cells were more uniformly stained than beta-cells. Similar results were obtained with adult rat islets, in which, again, there was a large range of staining intensity and many cells with low levels of PRL receptor. Rats on day 14 of pregnancy had an increased level of islet PRL receptor expression compared with age-matched control animals. There was also a decrease in cellular heterogeneity for PRL receptors, with nearly all cells having a uniformly high level of PRL receptor expression. JAK2, the tyrosine kinase associated with PRL receptors, was examined in Nb2 cells and islets. JAK2 immunoreactivity was detected at the cell membrane in very low levels in Nb2 cells. It was also found in numerous vesicular structures in the cytoplasm, where it colocalized with PRL receptors. A prominent feature of all cells was the presence of JAK2 in the nucleus, but not the nucleolus. In islets, JAK2 immunoreactivity was similarly observed in the nucleus of nearly all cells. However, the vesicular cytoplasmic location of JAK2 was less frequently observed and did not colocalize with PRL receptors. For comparison, JAK2 immunoreactivity was examined in several other tissues where it was detected in fibroblasts (endomysial and endoneurial cells), smooth muscle cells, and ganglion cells in the pancreas. JAK2 was notably absent from pancreas acinar cells, hepatocytes, skeletal muscle cells, and Schwann cells. This study demonstrates the presence of PRL receptors in islet beta- and alpha-cells, but not delta-cells. There was an increase in PRL receptor expression in islets during pregnancy, which is commensurate with the up-regulation of islet function. In addition, JAK2 immunoreactivity was detected in most islet cells and Nb2 node cells.
催乳激素、催乳素（PRL）和胎盘催乳素是胰岛素分泌和胰岛β细胞增殖的重要调节因子。在本研究中，我们使用保罗·凯利博士提供的PRL受体单克隆抗体，检测了朗格汉斯胰岛中PRL受体免疫反应性的存在情况。研究使用了从新生大鼠、成年大鼠和妊娠14天的大鼠分离的胰岛。通过免疫组织化学和激光扫描共聚焦显微镜对胰岛进行检查。在新生大鼠胰岛中，PRL受体在β细胞和α细胞中被观察到，但在δ细胞中未观察到。在胰岛β细胞和α细胞中，PRL受体的细胞染色存在异质性。一小部分细胞对PRL受体有强烈染色。然而，大多数细胞的染色强度要低得多，这表明大多数胰岛细胞的PRL受体水平较低。一般来说，α细胞的染色比β细胞更均匀。成年大鼠胰岛也得到了类似的结果，其中同样存在广泛的染色强度范围，许多细胞的PRL受体水平较低。与年龄匹配的对照动物相比，妊娠14天的大鼠胰岛PRL受体表达水平增加。PRL受体的细胞异质性也有所降低，几乎所有细胞都有均匀较高水平的PRL受体表达。在Nb2细胞和胰岛中检测了与PRL受体相关的酪氨酸激酶JAK2。在Nb2细胞的细胞膜上检测到极低水平的JAK2免疫反应性。在细胞质中的许多囊泡结构中也发现了JAK2，它与PRL受体共定位。所有细胞的一个突出特征是JAK2存在于细胞核中，而不存在于核仁中。在胰岛中，几乎所有细胞的细胞核中都同样观察到JAK2免疫反应性。然而，JAK2在细胞质中的囊泡位置较少被观察到，并且不与PRL受体共定位。为了进行比较，在其他几种组织中检测了JAK2免疫反应性，在胰腺中的成纤维细胞（肌内膜和神经内膜细胞）、平滑肌细胞和神经节细胞中检测到了JAK2。胰腺腺泡细胞、肝细胞、骨骼肌细胞和雪旺细胞中明显没有JAK2。本研究证明了PRL受体存在于胰岛β细胞和α细胞中，但不存在于δ细胞中。妊娠期间胰岛中PRL受体表达增加，这与胰岛功能的上调相一致。此外，在大多数胰岛细胞和Nb2节点细胞中检测到了JAK2免疫反应性。
