Bird C C, Robertson A M, Read J, Currie A R
J Pathol. 1977 Nov;123(3):145-56. doi: 10.1002/path.1711230304.
Glucocorticoid hormones penetrate rapidly into intact lymphoblastoid cells and are retained with the same high affinity and specificity as with cytoplasmic extracts. Optimal conditions for lethal glucocorticoid responses in vitro were determined for a series of human lymphoblastoid cell lines by using different glucocorticoid preparations, and steroid solvents and by varying the cell density. Kinetic studies revealed that lethal glucocorticoid effects are dose-dependent and that continuous exposure of cells to steroid is necessary for progression of lethal effects to occur. Even under optimal conditions, human lymphoblastoid cells only exhibit a marked cytolethal response to glucocorticoids at concentrations which greatly exceed both physiological and therapeutically attainable steroid levels. They are also greatly in excess of steroid levels required to saturate the cytoplasmic receptors of intact or disrupted lymphoblastoid cells. It is suggested that either lethal steroid mechanisms in vitro differ fundamentally from those in vivo or the pharmacological activity of glucocorticoids in vivo does not involve a direct cytolethal action.
糖皮质激素能迅速穿透完整的淋巴母细胞样细胞，并以与细胞质提取物相同的高亲和力和特异性被保留。通过使用不同的糖皮质激素制剂、类固醇溶剂并改变细胞密度，确定了一系列人淋巴母细胞样细胞系在体外产生致死性糖皮质激素反应的最佳条件。动力学研究表明，致死性糖皮质激素效应具有剂量依赖性，并且细胞持续暴露于类固醇是致死效应发生进展所必需的。即使在最佳条件下，人淋巴母细胞样细胞也仅在大大超过生理和治疗可达到的类固醇水平的浓度下才对糖皮质激素表现出明显的细胞致死反应。它们也大大超过了使完整或破裂的淋巴母细胞样细胞的细胞质受体饱和所需的类固醇水平。这表明，要么体外致死性类固醇机制与体内机制根本不同，要么糖皮质激素在体内的药理活性不涉及直接的细胞致死作用。
