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首页> 外文期刊>The biochemical journal >Heterogeneity of growth-hormone receptors detected with monoclonal antibodies to human growth hormone
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Heterogeneity of growth-hormone receptors detected with monoclonal antibodies to human growth hormone

机译:用人类生长激素单克隆抗体检测生长激素受体的异质性

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pThe specificity of hormone-receptor interactions has been examined with the aid of monoclonal antibodies (MABs) (EB1, EB2, QA68 and NA71) defining four non-overlapping antigenic determinants on human growth hormone (hGH). The results indicate that growth-hormone receptors in liver obtained from different sources differ with regard to their affinities and relative numbers; they may also differ with respect to the region of the growth-hormone molecule to which they bind. Antibody NA71 effectively inhibited hormone binding to all receptor preparations tested, although with various degrees of potency. Monoclonal antibody EB1 demonstrated a graded inhibition with respect to its ability to block 125I-hGH binding to receptors from various sources, the maximum inhibition being seen in receptor preparations from mouse and ovine liver and the minimum in rat liver. MABs EB2 and QA68 also showed various abilities to inhibit hormone-receptor interaction, depending on the origin of the receptor preparation. Furthermore, the receptor-binding characteristics of hormone-antibody complexes were dependent on whether the binding-site preparation was derived from pregnant, lactating or ‘normal’ animals. A particularly striking difference between the ability of hormone-MAB complexes to bind to receptors from different sources was seen for microsomes (microsomal fractions) derived from livers of animals of the ‘Little’ mouse strain. These animals become progressively obese, and it was shown that MABs were considerably more effective in inhibiting 125I-labelled hGH binding to microsomes from phenotypically obese mice than to those derived from their non-obese littermates. The results can be explained by the presence of multiple receptor types for GH, the relative proportions of which vary according to the physiological state of the animal, and possibly between species./p
机译:>已通过单克隆抗体(MAB)(EB1,EB2,QA68和NA71)检测了激素-受体相互作用的特异性,这些抗体定义了人类生长激素(hGH)上的四个非重叠抗原决定簇。结果表明,从不同来源获得的肝中生长激素受体的亲和力和相对数量有所不同。它们在结合的生长激素分子区域上也可能不同。抗体NA71有效抑制激素与所有测试受体的结合,尽管具有不同程度的效力。单克隆抗体EB1阻断125I-hGH与各种来源的受体结合的能力表现出分级抑制作用,最大抑制作用出现在小鼠和绵羊肝脏的受体制剂中,最小抑制作用在大鼠肝脏。 MAB EB2和QA68还显示出多种抑制激素与受体相互作用的能力,具体取决于受体制剂的来源。此外,激素-抗体复合物的受体结合特征取决于结合位点制剂是否来自妊娠,哺乳期或“正常”动物。对于来自“ Little”小鼠品系动物肝脏的微粒体(微粒体级分),激素-MAB复合物与不同来源的受体结合的能力之间存在特别明显的差异。这些动物逐渐肥胖,并且已经显示,MABs在抑制125I标记的hGH与表型肥胖小鼠的微粒体结合方面比与非肥胖同窝小鼠衍生的微粒体有效得多。 GH的多种受体类型可以解释这一结果,其相对比例根据动物的生理状态以及物种之间的生理状态而变化。

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