Exploring the mechanism of carbamazepine decreasing testosterone levels based on cAMP/PKA/CREB pathway.

IF 2.6 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY 3 Biotech Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI:10.1007/s13205-024-04156-7

Jingya Li, Ziao Liu, Min Pan, Li Li, Xiaohui Tong, Yajuan Wang, Bin Chen, Tongsheng Wang

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Abstract

The aim of this study was to explore the molecular mechanisms underlying carbamazepine (CBZ)-induced testicular toxicity and testosterone reduction in rats. For this purpose, Sprague-Dawley (SD) rats were intervened with 200 mg/kg CBZ for 12 weeks, and R2C cells were exposed to CBZ at concentrations of 0.5, 1 and 1.5 mM for 24 h. HE, Tunel, ELISA, immunofluorescence staining, RT-qPCR, and western blot were used to reveal the effects of CBZ on spermatozoa quality, testicular tissue structure, testosterone level and testosterone synthesis-related enzymes in rats. The results showed that CBZ significantly damaged the testicular tissue structure of rats, induced cell apoptosis, down-regulated the gene and protein expression levels of testosterone synthesis-related enzymes (STAR, TSPO, 17β-HSD and 3β-HSD), inhibited the expression of related proteins in the cAMP/PKA/CREB signalling pathway, and suppressed testosterone levels. In addition, the use of Db-cAMP (a PKA activator) significantly upregulated the protein expressions of PKA and p-CREB, evidently alleviated the CBZ-induced decrease in testosterone levels. In conclusion, CBZ induced testosterone resynthesis by inhibiting the cAMP/PKA/CREB pathway, affecting the expression of steroid synthesis-related enzymes and reducing testosterone levels.

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基于 cAMP/PKA/CREB 通路探索卡马西平降低睾酮水平的机制

本研究旨在探索卡马西平（CBZ）诱导大鼠睾丸毒性和睾酮减少的分子机制。研究采用HE、Tunel、ELISA、免疫荧光染色、RT-qPCR和Western blot等方法揭示了CBZ对大鼠精子质量、睾丸组织结构、睾酮水平和睾酮合成相关酶的影响。结果表明，CBZ能明显破坏大鼠的睾丸组织结构，诱导细胞凋亡，下调睾酮合成相关酶（STAR、TSPO、17β-HSD和3β-HSD）的基因和蛋白表达水平，抑制cAMP/PKA/CREB信号通路中相关蛋白的表达，抑制睾酮水平。此外，使用 Db-cAMP（一种 PKA 激活剂）可显著上调 PKA 和 p-CREB 蛋白表达，明显缓解 CBZ 诱导的睾酮水平下降。总之，CBZ 通过抑制 cAMP/PKA/CREB 通路，影响类固醇合成相关酶的表达，从而诱导睾酮的再合成，降低睾酮水平。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.