Urinary Oxalate Excretion Decreased in Androgen Receptor-Knockout Mice by Suppressing Oxalate Synthesis in the Liver
Urinary Oxalate Excretion Decreased in Androgen Receptor-Knockout Mice by Suppressing Oxalate Synthesis in the Liver
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DOI：
10.4236/oju.2015.58020
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Sayuri Takahashi;S. Aruga;Yoko Yamamoto;Takahiro Matsumoto
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文献类型：
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作者：
Sayuri Takahashi;S. Aruga;Yoko Yamamoto;Takahiro Matsumoto
男性草酸钙结石的发病率高于女性。我们使用 Cre-floxed 雄性雄激素受体敲除 (ARKO) 小鼠 (ARL−/Y) 和 floxed 小鼠 (ARL+/Y) 作为对照，评估了雄激素受体 (AR) 与尿草酸盐排泄之间的关联。给十四周大的 ARL-/Y 和 ARL+/Y 小鼠喂蒸馏水。然后将饮用水换成 0.5% 乙二醇 (EG)。在第 0、14 和 28 天测量尿草酸盐。在第 0 天和第 15 天评估小鼠 AP (CaOx)-indexMOUSE 中的尿钙、无机磷、柠檬酸盐、尿酸和草酸钙 (AP-CaOx) 离子活性产物。在第 28 天，收获肝脏以测量酶的 mRNA 表达。 EG 治疗后 14 和 28 天，AR L+/Y 小鼠的尿草酸盐排泄量显着高于 AR L−/Y 小鼠（p < 0.05）。由于AR L−/Y小鼠表现出睾丸萎缩和血清睾酮水平低，因此ARKO和对照小鼠均被切除睾丸并植入DHT颗粒（ARL−/Y-ORX-DHT和ARL+/Y-ORX-DHT），并进行与上述相同的实验。 14 和 28 天的 EG 负载导致 AR L+/Y -ORX-DHT 小鼠的排泄量显着高于 AR L−/Y -ORX-DHT 小鼠（p < 0.005）。 ARL+/Y-ORX-DHT 小鼠中的 AP(CaOx)-indexMOUSE 显着高于 ARL-/Y-ORX-DHT 小鼠。 ARKO 小鼠肝脏中乙醇酸氧化酶（GO）的 mRNA 表达水平低于对照小鼠。 AR 调节 EG 治疗后尿液中草酸盐的排泄，这可能与肝脏中通过 AR 途径激活的 GO 增加草酸盐合成有关。 * 通讯作者。
The incidence of calcium oxalate stone in men is higher than that in women. We evaluated the as- sociation between the androgen receptor (AR) and urinary oxalate excretion using Cre-floxed male androgen receptor-knockout (ARKO) mice (ARL−/Y) and floxed mice (ARL+/Y) as control. Four- teen-week-old ARL−/Y and ARL+/Y mice were fed distilled water. Drinking water was then swapped for 0.5% ethylene glycol (EG). Urinary oxalate was measured on days 0, 14, and 28. Urinary cal- cium, inorganic phosphorus, citrate, uric acid, and ion-actibity products of calcium oxalate (AP- CaOx) in mouse, AP (CaOx)-indexMOUSE, were evaluated on days 0 and 15. On day 28, livers were harvested to measure mRNA expression of enzymes. Urinary oxalate excretion was significantly higher in AR L+/Y than in AR L−/Y mice 14 and 28 days after EG treatment (p < 0.05). Since AR L−/Y mice exhibited atrophic testes and low serum testosterone, both ARKO and control mice were orchiec- tomized and implanted DHT pellets (ARL−/Y-ORX-DHT, and ARL+/Y-ORX-DHT), and the same expe- riments as above were performed. EG loading for 14 and 28 days resulted in significantly higher excretion in AR L+/Y -ORX-DHT mice than AR L−/Y -ORX-DHT mice (p < 0.005). AP(CaOx)-indexMOUSE was significantly higher in ARL+/Y-ORX-DHT mice than in ARL−/Y-ORX-DHT mice. mRNA expression le- vels of glycolate oxidase (GO) in liver were lower in ARKO mice than in control ones. AR modulates the excretion of oxalate in urine after EG treatment, which may be associated with increased oxa- late synthesis by activated GO in the liver via the AR pathway. * Corresponding author.