Receptor-mediated mitogenic action of prolactin in a rat lymphoma cell line.-猫眼课题宝

催乳素在大鼠淋巴瘤细胞系中受体介导的有丝分裂作用。

DOI：

发表时间：

1983

期刊：

Endocrinology

影响因子：

4.8

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

R. Shiu;H. Elsholtz;T. Tanaka,;H. Friesen;P. Gout;C. T. Beer;R. Noble

PRL和其他催乳激素是源自雌激素化的Noble（Nb）大鼠淋巴结的淋巴瘤细胞系中的有效有丝分裂原。目前的研究表明，这些细胞（指定Nb 2节点）拥有的受体，仅结合催乳激素。每个细胞大约有12，000个受体位点。Nb 2淋巴瘤细胞表现出的[125 I]碘-PRL结合动力学是不寻常的，因为PRL结合遵循双相模式。[125 I]碘-PRL结合在37 ℃下1小时内达到最大值，随后迅速下降。如果结合在氯喹（一种溶酶体促进剂）存在下进行，或者如果使用细胞匀浆进行结合，则未观察到这种模式。我们还研究了这些细胞中受体占用率和PRL反应幅度之间的关系。最大的生长刺激PRL发生时，只有35%的最大结合的PRL实现，这表明大多数的PRL结合位点可能是备用受体。这项研究还表明，Nb 2细胞中PRL受体的解离常数（Kd）为75 pM，比其他细胞类型中的受体高约20倍。6 pM的PRL在Nb 2细胞中产生半最大生长反应。针对PRL受体的抗体能够消除PRL诱导的Nb 2细胞增殖。在没有PRL的情况下，这些抗体单独可以诱导Nb 2细胞的增殖，模拟PRL的作用。二价（Fab）2片段，但不是单价Fab，也是有效的。这些观察结果表明，受体的抗体，或激素本身，可能通过交联细胞膜上的PRL受体启动生物反应，并认为PRL分子，或其片段，进入细胞内隔室是不必要的PRL的生物作用。

PRL and other lactogenic hormones are potent mitogens in a lymphoma cell line derived from a lymph node of an estrogenized Noble (Nb) rat. The present study demonstrates that these cells (designated Nb2 node) possess receptors that bind only lactogenic hormones. There are approximately 12,000 receptor sites per cell. The kinetics of binding of [125I]iodo-PRL exhibited by Nb2 lymphoma cells is unusual in that PRL binding follows a biphasic pattern. Binding of [125I]iodo-PRL reaches a maximum in 1 h at 37 C, followed by a rapid decline. This pattern was not observed if binding was carried out in the presence of chloroquine, a lysosomotropic agent, or if cell homogenate was used for binding. We also examined the relationship between receptor occupancy and the magnitude of PRL response in these cells. Maximal growth stimulation by PRL occurs when only 35% of the maximal binding of PRL is achieved, suggesting that a majority of the PRL binding sites may be spare receptors. This study also revealed that the dissociation constant (Kd) of the PRL receptors in Nb2 cells is 75 pM, approximately 20-fold higher than that of the receptors in other cell types. PRL at 6 pM produces a half-maximal growth response in the Nb2 cells. Antibodies against the PRL receptors are able to abolish the PRL-induced proliferation of Nb2 cells. In the absence of PRL, these antibodies alone can induce proliferation of Nb2 cells, mimicking the action of PRL. Divalent (Fab)2 fragments, but not monovalent Fab, were also effective. These observations suggest that antibodies to the receptor, or the hormone itself, initiate a biological response possibly by cross-linking PRL receptors on the cell membrane, and that the entry of the PRL molecule, or fragments of it, into the intracellular compartment is not necessary for the biological action of PRL.

Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor.