Fernández L, Boada L D, Luzardo O P, Zumbado M, López A, Díaz-Chico B N, Chirino R
Department of Clinical Sciences, Faculty of Health Sciences, University of Las Palmas de G.C., Spain.
Pharmacol Toxicol. 1995 Oct;77(4):264-9. doi: 10.1111/j.1600-0773.1995.tb01025.x.
Rat liver microsomes contain a single class of steroid binding sites, capable of binding various glucocorticoids and progesterone. In a previous article, we have described the in vitro interaction of several androgens with this binding site. Unlike natural androgens, the 17 alpha-alkyl derivatives stanozolol and danazol were capable of interacting with this binding site through a negative allosteric pattern. Now, the effects these steroids exert on the microsomal [3H]dexamethasone binding site have been studied in vivo. The administration of a single dose of stanozolol to rats provoked a significant reduction in the microsomal [3H]dexamethasone binding capacity. This effect was maximal two hr after stanozolol administration and persisted for six hr. The restoration of the [3H]dexamethasone binding level after stanozolol administration was dependent on protein synthesis, since it was blocked by the concomitant administration of cycloheximide. None of the other androgens tested (danazol, methyltestosterone, fluoxymesterone, and testosterone propionate) was capable of provoking a similar effect when administered 2 or 24 hr prior to sacrifice. In rats treated for seven days with a daily dose of diverse androgens and sacrificed 24 hr after the last treatment, none of the 17 alpha-alkyl androgens assayed provoked significant changes in the microsomal [3H]dexamethasone binding level, although stanozolol, danazol, and methyltestosterone provoked a significant increase in glucocorticoid receptor concentration. In contrast, the administration of testosterone propionate provoked a 50% reduction in the [3H]dexamethasone binding level without causing changes in the glucocorticoid receptor concentration. These results provide new evidence on the existence of different effects on the liver of 17 alpha-alkyl androgens, compared to the effects produced by natural androgens.
大鼠肝微粒体含有一类单一的类固醇结合位点，能够结合各种糖皮质激素和孕酮。在之前的一篇文章中，我们描述了几种雄激素与该结合位点的体外相互作用。与天然雄激素不同，17α-烷基衍生物司坦唑醇和达那唑能够通过负变构模式与该结合位点相互作用。现在，已在体内研究了这些类固醇对微粒体[3H]地塞米松结合位点的影响。给大鼠单次注射司坦唑醇会导致微粒体[3H]地塞米松结合能力显著降低。这种作用在注射司坦唑醇后2小时达到最大，并持续6小时。司坦唑醇给药后[3H]地塞米松结合水平的恢复依赖于蛋白质合成，因为同时给予环己酰亚胺会阻断这种恢复。在处死前2小时或24小时给予其他所测试的雄激素（达那唑、甲基睾酮、氟甲睾酮和丙酸睾酮），均不能引发类似的效应。在每天给予不同雄激素连续治疗7天、最后一次治疗后24小时处死的大鼠中，所检测的17α-烷基雄激素均未引起微粒体[3H]地塞米松结合水平的显著变化，尽管司坦唑醇、达那唑和甲基睾酮引起了糖皮质激素受体浓度的显著增加。相比之下，给予丙酸睾酮会导致[3H]地塞米松结合水平降低50%，而不会引起糖皮质激素受体浓度的变化。这些结果为17α-烷基雄激素与天然雄激素对肝脏产生的不同影响提供了新的证据。
