Aston R, Holder A T, Preece M A, Ivanyi J
J Endocrinol. 1986 Sep;110(3):381-8. doi: 10.1677/joe.0.1100381.
Monoclonal antibodies of certain epitope specificity have been shown to produce a marked dose-dependent enhancement of the somatogenic and lactogenic activity of human GH (hGH). Two antibodies (EB1 and EB2), binding to distinct antigenic determinants and expressed on both hGH and human chorionic somato-mammotrophin (hCS), significantly enhanced the hGH-stimulated uptake of 35S-labelled sulphate into cartilage. Similarly, these antibodies enhanced the lactogenic activity of both hGH and hCS in the pigeon crop sac test. Two hGH specific monoclonal antibodies (QA68 and NA71), defining a further two epitopes, exhibited only modest enhancing or inhibitory activity in these assays, whereas the binding of certain combinations of monoclonal antibodies resulted in either reversal of enhancement or inhibition of hormone activity. Univalent antibody fragments derived from EB1 were as enhancing as the intact antibody indicating that bivalency dependent mechanisms were not involved in the phenomenon. Enhancing monoclonal antibodies were relatively poor inhibitors of 125I-labelled hGH binding to liver microsomal receptors, which is in contrast with their previously described property of potent suppression of hGH interaction with lymphoid cell receptors. It is tentatively concluded that 'restriction' of hormone binding to particular hGH receptors, relevant to somatic growth or lactogenic activity, may play a role in the enhancement phenomenon of hGH in vivo.
某些具有特定表位特异性的单克隆抗体已被证明可显著增强人生长激素（hGH）的促生长和催乳活性，且呈明显的剂量依赖性。两种抗体（EB1和EB2），它们与不同的抗原决定簇结合，且在hGH和人绒毛膜促生长催乳素（hCS）上均有表达，能显著增强hGH刺激的35S标记硫酸盐进入软骨的摄取。同样，这些抗体在鸽嗉囊试验中增强了hGH和hCS的催乳活性。另外两种定义了不同表位的hGH特异性单克隆抗体（QA68和NA71），在这些试验中仅表现出适度的增强或抑制活性，而某些单克隆抗体组合的结合则导致增强作用的逆转或激素活性的抑制。源自EB1的单价抗体片段与完整抗体一样具有增强作用，这表明该现象不涉及双价依赖性机制。增强型单克隆抗体对125I标记的hGH与肝微粒体受体结合的抑制作用相对较弱，这与其先前描述的对hGH与淋巴细胞受体相互作用的强效抑制特性形成对比。初步得出结论，与体细胞生长或催乳活性相关的激素与特定hGH受体的“限制”结合可能在hGH体内增强现象中起作用。
