Research in Molecular Mechanism of Prolactin Binding to its Receptor

催乳素与其受体结合的分子机制研究

• 批准号: 03454096
• 负责人: SAKAI Senkiti
• 金额: $ 3.07万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454096/
• 关键词: prolactin; prolactin receptor; plasma membrane receptor; mammary gland; hormone-induced dissociation; negative cooperativity; Scatchard plot; Hill plot; レセプタ-; 解離機構; 高濃度プロラクチン

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.

我们已经明确了乳腺催乳素(PRL)受体的两点：(1)PRL以剂量依赖的方式加速PRL与其受体的解离。Scatchard分析表明，该反应不是一个简单的双分子反应。希尔的情节是非线性的。当PRL高于30 ng/ml时，Hill系数由1.0变为0.7。使用PRL预加载的受体，该受体在PRL诱导的解离后保持活跃以进行关联。由于PRL加速了PRL的结合反应，推测高水平的PRL可以主动地产生激素信号。在激素水平过高或异常升高的条件下，负的协同性具有重要的生物学意义。(2)与细胞受体结合的PRL在酸处理下以摩尔浓度依赖的方式解离，而不是pH依赖的方式。产后酸敏感受体与酸不敏感受体的比例无明显变化。通过亚细胞膜的酸处理，约80%的PRL与胞浆和胞内受体结合，分别是酸敏感和酸不敏感的。我们得出结论，质膜PRL受体是固有的酸敏感的，并独立调节。

项目成果

SUZUKI,M.,KOHMOTO.K.,SAKAI,S.: "Radioreceptor assay of serum prolactin using mitrocellulose membraneーimmobilized prolactin receptor" Analytical Biochemistry. 200. 42-46 (1992)

SUZUKI, M., KOHMOTO.K., SAKAI, S.：“使用纤维纤维素膜固定催乳素受体进行血清催乳素放射受体测定”分析生物化学。 200. 42-46 (1992)

SAKAI Senkiti: "Ebbect of hormones on dissociation ofp rolactin from the rabbit mammary gland prolactin receptor" Biochenical Journal. 279. 461-465 (1991)

SAKAI Senkiti：“激素对催乳素与兔乳腺催乳素受体解离的影响”生物化学杂志。

酒井 仙吉: "プロラクチン受容体による乳腺機能の調節ー受容体遺伝子の構造ー" 日本畜産学会報. 63. 1203-1208 (1992)

Senkichi Sakai：“催乳素受体对乳腺功能的调节 - 受体基因的结构”日本动物学会通报 63. 1203-1208 (1992)。

SUZUSI Maki,KOHMOTO Kaoru,SAKAI Senkiti: "Radioreceptor assay of serum prola ctin using nitrocell a lose membrane-immobilized mammarye prolachn receptor" Analytical Biochemistny. 200. 42-46 (1991)

SUZUSI Maki、KOHMOTO Kaoru、SAKAI Senkiti：“使用硝基细胞（一种失膜固定的乳腺催乳素受体）对血清催乳素进行放射受体测定”分析生物化学。

SAKAI Senkiti: "Ebbect of administration of a cfinomycin D and protein-synthesis inhibitors on the binding of prolactin to the mammey gland receptor" Animal Scieuce and Technologh. 63. 1-7 (1992)

SAKAI Senkiti：“施用奇霉素 D 和蛋白质合成抑制剂对催乳素与乳腺受体结合的影响”动物科学与技术。