MECHANISM OF ANDROGEN-INDUCED THYMOLYSIS IN RATS
MECHANISM OF ANDROGEN-INDUCED THYMOLYSIS IN RATS
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DOI：
10.1210/en.136.11.4887
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发表时间：
1995-11-01
期刊：
影响因子：
4.8
通讯作者：
SUNDARAM, K
中科院分区：
文献类型：
--
作者：
KUMAR, N;SHAN, LX;SUNDARAM, K
为了研究雄激素诱导的胸腺溶解的机制，将各种雄激素，包括睾酮（T）、19-去甲睾酮和7α-甲基-19-去甲睾酮（MENT）的作用与雌二醇和地塞米松（DEX）对完整、去势和肾上腺切除的雄性大鼠进行比较。基于类固醇质量的胸腺退化效力比较显示，DEX 是最有效的，其次是雌二醇和雄激素。在雄激素中，MENT 是最有效的，其次是去甲睾酮和 T，其顺序与它们对肌肉的合成代谢效力相似。由于同时服用芳香酶抑制剂或 5-还原酶抑制剂不会改变 T 和 MENT 的胸腺溶解作用，因此得出结论，雄激素的作用不是通过其转化为雌激素或 5α 还原代谢物来介导的。糖皮质激素受体参与雄激素作用被排除，因为米非司酮（一种抗糖皮质激素）可阻断 DEX 诱导的胸腺退化，但不能阻断 T 或 MENT 诱导的胸腺退化。氟他胺是一种抗雄激素药物，可显着阻断 T 和 MENT 的胸腺溶解作用，为这一结论提供了进一步的支持。这表明雄激素的胸腺溶解作用是通过雄激素受体（AR）介导的内在特性。结合测定证明了胸腺中 AR 的存在，并且通过逆转录酶-聚合酶链反应证明了 AR 信使 RNA (mRNA) 的存在。胸腺中 AR mRNA 的定量逆转录酶-聚合酶链反应显示，胸腺上皮细胞中的 AR mRNA 比胸腺细胞中多 6 倍。然而，上皮细胞仅代表胸腺的一小部分。因此，推测雄激素通过刺激胸腺上皮细胞分泌因子来产生其胸腺溶解作用，进而导致胸腺退化。
To investigate the mechanism of androgen-induced thymolysis, the effects of various androgens, including testosterone (T), 19-nortestosterone, and 7 alpha-methyl-19-nortestosterone (MENT), were compared with those of estradiol and dexamethasone (DEX) in intact, castrated, and adrenalectomized male rats. The potency comparisons on thymus regression, based on mass of steroids, showed DEX to be the most potent, followed by estradiol and the androgens. Among the androgens, MENT was the most potent, followed by nortestosterone and T, an order similar to their anabolic potency on muscle. As the thymolytic effects of T and MENT were not altered by the concomitant administration of an aromatase inhibitor or a 5-reductase inhibitor, it was concluded that the effects of androgens were not mediated by their conversion to estrogens or 5 alpha-reduced metabolites. involvement of glucocorticoid receptors in androgen action was excluded because mifepristone (an antiglucocorticoid) blocked DEX-induced, but not T-or MENT-induced, thymus regression. Flutamide, an antiandrogen, significantly blocked the thymolytic effect of T and MENT, providing further support for this conclusion. This suggested that the thymolytic action of androgens is an intrinsic property mediated via androgen receptors (AR). The occurrence of AR in the thymus was demonstrated by binding assays and the presence of AR messenger RNA (mRNA) by reverse transcriptase-polymerase chain reaction. Quantitative reverse transcriptase-polymerase chain reaction for AR mRNA in the thymus showed 6-fold more AR mRNA in the thymic epithelial cells than in the thymocytes. However, epithelial cells represent only a small fraction of the thymus. Hence, it is hypothesized that the androgens produce their thymolytic effects by stimulating the secretion of a factor(s) by the thymic epithelial cells that, in turn, causes regression of the thymus.