Section of Experimental Endocrinology, Department of Pharmacology, São Paulo, Brazil.
Andrology. 2013 Sep;1(5):670-81. doi: 10.1111/j.2047-2927.2013.00103.x. Epub 2013 Jul 9.
Varicocoele is an important cause of male infertility. Normal male reproductive function and fertility depends on a delicate balance between androgen receptor (AR) and the classic oestrogen receptors ESR1 (ERα) and ESR2 (ERβ). Using a model of surgically induced varicocoele in rats, this study aimed to investigate the effects of varicocoele on the expression of AR, ESR1, ESR2 and G-protein coupled oestrogen receptor (GPER). Varicocoele did not affect the mRNA and protein expression of ESR1 and ESR2 in both testes. Varicocoele did not affect the mRNA and protein expression of GPER in the right testis, but slightly reduced the mRNA and increased the protein levels in the left testis. Varicocoele did not affect the mRNA for AR, but reduced the protein levels in both testes. A proteomic approach was used in an attempt to find differentially expressed targets with possible correlation with AR downregulation. Varicocoele caused the differential expression of 29 proteins. Six proteins were upregulated, including the receptor for activated C kinase 1 (RACK1), and 23 were downregulated, including dihydrolipoamide dehydrogenase, alpha-enolase and pyrophosphatase 1. Western blot analysis confirmed that varicocoele upregulated the expression of RACK1, a protein involved with tyrosine phosphorylation and regulation of AR transcriptional activity, AR metabolism and dynamics of the blood-testis barrier. In conclusion, this study suggests that varicocoele affects mechanisms that control AR expression and function. This regulation of AR may play an important role in the varicocoele-induced testicular dysfunction. Furthermore, varicocoele downregulates several other proteins in the testis that may be useful markers of spermatozoa function and male infertility.
精索静脉曲张是男性不育的一个重要原因。正常男性生殖功能和生育能力依赖于雄激素受体 (AR) 与经典雌激素受体 ESR1 (ERα) 和 ESR2 (ERβ) 之间的微妙平衡。本研究采用大鼠精索静脉曲张手术模型，旨在探讨精索静脉曲张对 AR、ESR1、ESR2 和 G 蛋白偶联雌激素受体 (GPER) 表达的影响。精索静脉曲张对双侧睾丸 ESR1 和 ESR2 的 mRNA 和蛋白表达均无影响。精索静脉曲张对右侧睾丸 GPER 的 mRNA 和蛋白表达无影响，但轻度降低左侧睾丸的 mRNA 表达，增加其蛋白水平。精索静脉曲张不影响 AR 的 mRNA 表达，但降低双侧睾丸的蛋白水平。本研究采用蛋白质组学方法试图寻找与 AR 下调可能相关的差异表达靶点。精索静脉曲张导致 29 种蛋白的差异表达。其中 6 种蛋白上调，包括蛋白激酶 C 激活受体 1 (RACK1)，23 种蛋白下调，包括二氢硫辛酰胺脱氢酶、α-烯醇化酶和焦磷酸酶 1。Western blot 分析证实，精索静脉曲张上调了 RACK1 的表达，RACK1 是一种与 AR 转录活性的酪氨酸磷酸化和调节、AR 代谢以及血睾屏障动力学有关的蛋白。综上所述，本研究表明精索静脉曲张影响控制 AR 表达和功能的机制。AR 的这种调节可能在精索静脉曲张引起的睾丸功能障碍中发挥重要作用。此外，精索静脉曲张还下调了睾丸中的其他几种蛋白，这些蛋白可能是精子功能和男性不育的有用标志物。
