Pugeat M M, Dunn J F, Nisula B C
J Clin Endocrinol Metab. 1981 Jul;53(1):69-75. doi: 10.1210/jcem-53-1-69.
This report describes the binding of 70 synthetic compounds to both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG). The ability of each compound to displace [3H]testosterone from TeBG and [3H]cortisol from CBG adsorbed from a plasma pool onto a solid phase matrix of Concanavalin A-Sepharose was determined under equilibrium conditions at physiological pH and temperature. From these data, the association constants of the compounds for binding to both TeBG and CBG were calculated and used to predict whether endogenous steroid transport would be altered by the therapeutic administration of the drug. Computer simulation predicted that by interacting with TeBG, therapeutic levels of danazol, methyltestosterone, fluoxymesterone, and norgestrel could displace 83%, 48%, 43%, and 16%, respectively, of the concentration of testosterone bound to TeBG in a normal man. Similarly, by interacting with CBG, therapeutic levels of prednisolone could decrease the concentration of cortisol bound to CBG by approximately 32% in both men and women, and despite relatively low affinity binding to TeBG (5 X 10(5) M-1), prednisolone could also displace small amounts of testosterone from TeBG. These results indicate that binding to steroid transport proteins should be considered among the in vivo effects of drugs on endogenous steroid hormone levels.
本报告描述了70种合成化合物与睾酮结合球蛋白（TeBG）和皮质类固醇结合球蛋白（CBG）的结合情况。在生理pH值和温度的平衡条件下，测定了每种化合物从吸附在伴刀豆球蛋白A - 琼脂糖固相基质上的血浆池中置换[³H]睾酮从TeBG以及[³H]皮质醇从CBG的能力。根据这些数据，计算了化合物与TeBG和CBG结合的缔合常数，并用于预测药物的治疗性给药是否会改变内源性类固醇的转运。计算机模拟预测，通过与TeBG相互作用，达那唑、甲基睾酮、氟甲睾酮和炔诺孕酮的治疗水平分别可置换正常男性中与TeBG结合的睾酮浓度的83%、48%、43%和16%。同样，通过与CBG相互作用，泼尼松龙的治疗水平在男性和女性中均可使与CBG结合的皮质醇浓度降低约32%，并且尽管泼尼松龙与TeBG的亲和力相对较低（5×10⁵ M⁻¹），但它也可从TeBG中置换少量睾酮。这些结果表明，在药物对内源性类固醇激素水平的体内作用中，应考虑与类固醇转运蛋白的结合。
