Abstract：
Thymic atrophy affects T cell generation and migration to the periphery, thereby affecting T cell pool diversity. However, the mechanisms underlying thymic atrophy have not been fully elucidated. Here, gonadotropin-releasing hormone (GnRH) immunization and surgical castration did not affect thymocyte proliferation, but significantly reduced the apoptosis and increased the survival rate of CD4-CD8-, CD4+CD8+, CD4+CD8-, and CD4-CD8+ thymocytes. Following testosterone supplementation in rats subjected to GnRH immunization and surgical castration, thymocyte proliferation remained unchange, but the apoptosis of CD4-CD8-, CD4+CD8+, CD4+CD8-, and CD4-CD8+ thymocytes significantly increased. Transcriptome analyses of the thymus after GnRH immunization and surgical castration showed a significant reduction in the thymus\'s response to corticosterone. Cholesterol metabolism and the synthesis and secretion of corticosterone were significantly reduced. Analysis of the enzyme levels involved in the corticosterone synthesis pathway revealed that corticosterone synthesis in thymocytes was significantly reduced after GnRH immunization and surgical castration, whereas exogenous testosterone supplementation relieved this process. Testosterone promoted thymocyte apoptosis in a concentration-dependent manner, and induced corticosterone secretion in vitro. Blocking the intracellular androgen receptor (AR) signaling pathway did not significantly affect thymocyte apoptosis, but blocking the glucocorticoid receptor (GR) signaling pathway significantly reduced it. Our findings indicate that testosterone regulates thymus remodeling by affecting corticosterone synthesis in thymocytes, which activates GR signal transduction and promotes thymocyte apoptosis.
摘要：
胸腺萎缩影响T细胞的产生和向外周的迁移，从而影响T细胞池的多样性。然而,胸腺萎缩的潜在机制尚未完全阐明。这里,促性腺激素释放激素（GnRH）免疫和手术去势不影响胸腺细胞增殖，但显着减少了细胞凋亡并增加了CD4-CD8-的存活率，CD4+CD8+,CD4+CD8-,和CD4-CD8+胸腺细胞。在接受GnRH免疫和手术去势的大鼠中补充睾酮后，胸腺细胞增殖保持不变，但CD4-CD8-细胞凋亡,CD4+CD8+,CD4+CD8-,CD4-CD8+胸腺细胞明显增多。GnRH免疫和手术去势后胸腺的转录组分析显示胸腺对皮质酮的反应显著降低。胆固醇代谢和皮质酮的合成和分泌明显减少。对皮质酮合成途径所涉及的酶水平的分析显示，在GnRH免疫和手术去势后，胸腺细胞中的皮质酮合成显著减少，而外源性睾酮补充缓解了这一过程。睾酮以浓度依赖性方式促进胸腺细胞凋亡，并在体外诱导皮质酮分泌。阻断细胞内雄激素受体(AR)信号通路并不显著影响胸腺细胞凋亡,但阻断糖皮质激素受体（GR）信号通路会显著降低。我们的发现表明，睾酮通过影响胸腺细胞中皮质酮的合成来调节胸腺重塑，激活GR信号转导并促进胸腺细胞凋亡。
