Sakal E, Robertson M C, Chapnik-Cohen N, Tchelet A, Gertler A
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot, Israel.
Recept Signal Transduct. 1996;6(1):35-42.
Rat placental lactogen-I (rPL-I), expressed in rat uteri at midpregnancy, belongs to the GH/PRL/cytokine family of hormones (Wallis, 1992), all members of which exhibit a similar mechanism of receptor activation. Lactogenic activity of rPL-I as determined by Nb2 lymphoma cell bioassay was slightly higher than that of hGH. rPL-I was capable also of stimulating beta-casein production in mouse HC-11 cells. Competitive binding experiments using [125I]hGH or [125I]bPL and purified prolactin receptor extracellular domains (PRLR-ECDs) from rat (r), rabbit (rb), and bovine (b) showed rPL-I to be 12, 40, and 7-fold, respectively, less effective than hGH when competing with [125I]hGH. Displacement of [125I]bPL by rPL-I from rPRLR-ECD and rbPRLR-ECD was also 4-, and 30-fold less effective, respectively, than that by bPL. rPL-I did not compete at all with [125I]bPL for binding to bPRLR-ECD. In contrast, competitive binding experiments with [125I]hGH to a microsomal fraction of Nb2 cells showed rPL-I to be slightly more active than hGH. The stoichiometries of the complexes formed by rPL-I with rbPRLR-ECD, rPRLR-ECD, and bPRLR-ECD were studied by gel filtration. Whereas a 1:1 complex was formed between rPL-I and rPRLR-ECD and rbPRLR-ECD, no complex could be detected between rPL-I and bPRLR-ECD. The present results support the hypothesis that transient forms of a homodimer complex may be sufficient to initiate the biological signal, despite its short half-life.
大鼠胎盘催乳素-I（rPL-I）在妊娠中期的大鼠子宫中表达，属于激素的生长激素/催乳素/细胞因子家族（沃利斯，1992年），该家族所有成员都表现出相似的受体激活机制。通过Nb2淋巴瘤细胞生物测定法测定，rPL-I的催乳活性略高于hGH。rPL-I还能够刺激小鼠HC-11细胞中β-酪蛋白的产生。使用[125I]hGH或[125I]bPL以及来自大鼠（r）、兔（rb）和牛（b）的纯化催乳素受体细胞外结构域（PRLR-ECD）进行的竞争性结合实验表明，当与[125I]hGH竞争时，rPL-I与hGH相比，其效力分别低12倍、40倍和7倍。rPL-I从rPRLR-ECD和rbPRLR-ECD中取代[125I]bPL的效力也分别比bPL低4倍和30倍。rPL-I与[125I]bPL完全不竞争结合bPRLR-ECD。相反，用[125I]hGH与Nb2细胞的微粒体部分进行的竞争性结合实验表明，rPL-I的活性略高于hGH。通过凝胶过滤研究了rPL-I与rbPRLR-ECD、rPRLR-ECD和bPRLR-ECD形成的复合物的化学计量。虽然rPL-I与rPRLR-ECD和rbPRLR-ECD之间形成了1:1的复合物，但在rPL-I与bPRLR-ECD之间未检测到复合物。目前的结果支持这样一种假设，即同二聚体复合物的瞬时形式可能足以启动生物信号，尽管其半衰期很短。
