Khadijah Ramli Nur Siti, Giribabu Nelli, Salleh Naguib
Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Steroids. 2018 Oct;138:117-133. doi: 10.1016/j.steroids.2018.06.012. Epub 2018 Jul 10.
Effects of testosterone on expression and functional activity of ENaC, CFTR and NHE in vas deferens were investigated.
Orchidectomized, adult male rats were given 125 and 250 μg/kg/day testosterone subcutaneously, with or without flutamide and finasteride for seven consecutive days. At the end of the treatment, rats were anesthetized and vas deferens were perfused. Changes in vas deferens fluid secretion rate, pH, HCO, Cl and Na concentrations were recorded in the presence of amiloride and Cftr inh-172. Rats were then sacrificed and vas deferens were harvested and subjected for molecular biological analysis.
Testosterone treatment caused the fluid pH and HCO concentrations to decrease but secretion rate, Cl and Na concentrations to increase, where upon amiloride administration, the pH and HCO concentration increased but Cl and Na concentrations further increased. In testosterone-treated rats, administration of Cftr inh-172 caused all fluid parameters to decrease. In testosterone-treated rats co-administered with flutamide or finasteride, pH and HCO concentration increased but fluid secretion rate, Cl and Na concentrations decreased and these parameters were not affected by amiloride or Cftr inh-172 administration. Under testosterone influence, CFTR and γ-ENaC were highly expressed at the apical membrane while NHE-1 and 4 were highly expressed at the basolateral membrane of vas deferens epithelium. Meanwhile, NHE-2 and 3 were highly expressed at the apical membrane.
Differential expression of ENaC, CFTR and NHE in vas deferens under testosterone influence indicated the important role of these transporters in creating optimal fluid microenvironment that is essential for preserving male fertility.
研究了睾酮对输精管中上皮钠通道（ENaC）、囊性纤维化跨膜传导调节因子（CFTR）和钠氢交换体（NHE）表达及功能活性的影响。
对成年雄性去势大鼠皮下注射125和250μg/kg/天的睾酮，连续7天，同时给予或不给予氟他胺和非那雄胺。治疗结束时，将大鼠麻醉并对输精管进行灌注。在存在阿米洛利和Cftr inh - 172的情况下，记录输精管液体分泌速率、pH值、碳酸氢根（HCO）、氯离子（Cl）和钠离子（Na）浓度的变化。然后处死大鼠，摘取输精管并进行分子生物学分析。
睾酮治疗导致液体pH值和HCO浓度降低，但分泌速率、Cl和Na浓度升高，给予阿米洛利后，pH值和HCO浓度升高，但Cl和Na浓度进一步升高。在睾酮治疗的大鼠中，给予Cftr inh - 172导致所有液体参数降低。在与氟他胺或非那雄胺联合给药的睾酮治疗大鼠中，pH值和HCO浓度升高，但液体分泌速率、Cl和Na浓度降低，且这些参数不受阿米洛利或Cftr inh - 172给药的影响。在睾酮影响下，CFTR和γ-ENaC在输精管上皮细胞顶端膜高度表达，而NHE - 1和4在基底外侧膜高度表达。同时，NHE - 2和3在顶端膜高度表达。
在睾酮影响下输精管中ENaC、CFTR和NHE的差异表达表明这些转运蛋白在创造维持男性生育能力所必需的最佳液体微环境中起重要作用。
