Research in Molecular Mechanism of Prolactin Binding to its Receptor

我们已经清除了两个点在乳腺催乳素（PRL）受体。(1)催乳素可剂量依赖性地加速催乳素与受体的解离. Scatchard分析表明，该反应不是简单的双分子反应。希尔图是非线性的。当PRL高于30 ng/ml时，Hill系数从1.0变为0.7。使用PRL预载受体，受体在PRL诱导的解离后保持活性。由于PRL加速了PRL结合反应，因此推测高水平的PRL可以主动产生激素信号。负协同效应在激素水平异常升高的条件下具有重要的生物学意义。(2)与细胞受体结合的PRL被酸以摩尔浓度依赖的方式而不是pH依赖的方式解离。酸敏感受体与酸不敏感受体的比值在分娩后独立变化。通过酸处理亚细胞膜，约80%的PRL与质膜和细胞内膜受体结合分别是酸敏感和酸不敏感的。我们的结论是，质膜PRL受体本质上是酸敏感和调节独立。

We have cleared two points in the mammary prolactin (PRL) receptor.(1) PRL accelerated the dissociation of PRL from its receptor in a dose- dependent manner. Scatchard analysis revealed that this reaction is not a simple bimolecular reaction. The Hill plot was non-linear. At PRL higher than 30 ng/ml, the Hill coeficient changed from 1.0 to 0.7. Using the PRL-preloaded receptor, the receptor remained active for association after PRL-induced dissociation. As PRL accelerated the PRL-binding reaction, it was speculated that PRL at high levels can actively generate a hormonal signal. Negative cooperativity is of much biological importance under conditions where levels of hormone are elevated exceedingly or abnormally.(2) PRL bound to the cell receptor was dissociated by the treatment with acid in a molarity-dependent manner rather than pH-dependent. The ratio of acid-sensitive to acid-insensitive receptor changed independently after parturiton. By acid treatment of subcellular membranes, about 80% of PRL bound with plasma and intracellular membrane receptors were acid-sensitive and acid-insensitive, respectively. We concluded that plasma membrane PRL receptor is intrinsically acid-sensitive and regulated independently.