Sasson S, Mayer M
Endocrinology. 1981 Mar;108(3):760-6. doi: 10.1210/endo-108-3-760.
The potent androgens testosterone and 5 alpha-dihydrotestosterone, but not the inactive androgens etiocholanolone and androsterone, display antiglucocorticoid activity in rat thymus-derived lymphocytes. At a concentration of 10(-5) M, the potent androgens markedly lower the in vitro cytolytic response of isolated thymic lymphocytes to 10(-8) M dexamethasone. AT 2.5 X 10(-5) M, these androgens completely prevent the inhibition produced by 5 X 10(-8) M dexamethasone on 2-deoxyglucose uptake and uridine uptake and incorporation in isolated thymic lymphocytes. In the cytosol fraction obtained from rat thymus homogenate, the active androgens competitively inhibit the binding of [3H]dexamethasone to glucocorticoid-specific receptors with Ki values of 1.2 X 10(-6) and 2.5 X 10(-6) M for testosterone and 5 alpha-dihydrotestosterone, respectively. Thymus-derived lymphocytes and nuclei isolated from these cells exhibit binding of [3H]dexamethasone. The bound dexamethasone is avidly displaced by an excess of nonradioactive dexamethasone as well as by nonradioactive testosterone or 5 alpha-dihydrotestosterone. In contrast to their antiglucocorticoid activity in vitro, these androgens fail to elicit antiglucocorticoid activity when administered in vivo. This work shows that androgens are potent antiglucocorticoids in vitro due to competition with the active glucocorticoid on binding to cytoplasmic and nuclear receptor sites.
强效雄激素睾酮和5α - 双氢睾酮，而非无活性的雄激素本胆烷醇酮和雄酮，在大鼠胸腺来源的淋巴细胞中表现出抗糖皮质激素活性。在浓度为10(-5) M时，强效雄激素显著降低分离的胸腺淋巴细胞对10(-8) M地塞米松的体外细胞溶解反应。在2.5×10(-5) M时，这些雄激素完全阻止5×10(-8) M地塞米松对分离的胸腺淋巴细胞中2 - 脱氧葡萄糖摄取、尿苷摄取及掺入的抑制作用。在从大鼠胸腺匀浆获得的胞质溶胶部分中，活性雄激素竞争性抑制[3H]地塞米松与糖皮质激素特异性受体的结合，睾酮和5α - 双氢睾酮的Ki值分别为1.2×10(-6)和2.5×10(-6) M。胸腺来源的淋巴细胞及从这些细胞分离出的细胞核表现出[3H]地塞米松的结合。结合的地塞米松能被过量的非放射性地塞米松以及非放射性睾酮或5α - 双氢睾酮强烈取代。与它们在体外的抗糖皮质激素活性相反，这些雄激素在体内给药时未能引发抗糖皮质激素活性。这项研究表明，由于与活性糖皮质激素竞争结合细胞质和细胞核受体位点，雄激素在体外是强效抗糖皮质激素。
