Testosterone regulates thymic remodeling by activating glucocorticoid receptor signaling pathway to accelerate thymocyte apoptosis in male rats

文献类型： 外文期刊

第一作者： Li, Dong

作者： Li, Dong;Yao, Huan;Cao, Xiaohan;Han, Xingfa;Zeng, Xianyin;Song, Tianzeng

作者机构：

关键词： GnRH immunization; Surgical castration; Testosterone; Corticosterone; Apoptosis

期刊名称：JOURNAL OF REPRODUCTIVE IMMUNOLOGY （ 影响因子：2.9； 五年影响因子：3.3 ）

ISSN： 0165-0378

年卷期： 2024 年 164 卷

页码：

收录情况： SCI

摘要： 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, gonadotropinreleasing 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.

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