Miyajima Jiro, Hayashi Tokumasa, Saito Koujiro, Iida Shizuka, Matsuoka Kei
Department of Urology, Kurume University School of Medicine, Kurume, Japan.
Kurume Med J. 2010;57(3):73-80. doi: 10.2739/kurumemedj.57.73.
It is well known that the incidence of urinary stones is higher in men than women. Although it is believed that the lower incidence of urinary stones in women is due to a protective effect of estrogen, the mechanisms remain unclear. To clarify the relation between female sex hormones and stone matrix protein, we examined the interaction of estrogen receptor-α (ERα), estrogen receptor-related receptor-α (ERRα), and stone matrix protein osteopontin (OPN) in a rat hyperoxaluric model and in primary cultured rat kidney cells. Adult female Wistar rats were divided into 6 groups. Groups 1 and 4 consisted of normal females, Groups 2 and 5 consisted of ovariectomized females, and Groups 3 and 6 consisted of ovariectomized females receiving female sex hormone supplements. Groups 1-3 were administered distilled water, while groups 4-6 were administered 0.5% ethyleneglycol (EG). Moreover, rat kidney primary cultured cells were examined after treatment with female sex hormones under various conditions. The expressions of ERα, ERRα and OPN-mRNA in whole kidney and primary cultured cells were examined using Real-Time PCR. The expressions of OPN and ERRα-mRNA were suppressed by ovariectomy. Supplementation with female sex hormones increased the expression of OPN and ERRα-mRNA. In contrast, the expression of ERα-mRNA was increased by ovariectomy and suppressed by supplementation with female sex hormones. The results of the mRNA expression in primary cultured cells matched those in the hyperoxaluric model rats. Although the reason for the difference in expression between ERα and ERRα-mRNA is unclear, estrogen may regulates OPN expression through ERα and/or ERRα, either independently or in combination. Moreover, the decrease of OPN induced by removal of estrogen may increase urinary stones in postmenopausal women.
众所周知，尿石症的发病率男性高于女性。虽然人们认为女性尿石症发病率较低是由于雌激素的保护作用，但其机制仍不清楚。为了阐明女性性激素与结石基质蛋白之间的关系，我们在大鼠高草酸尿模型和原代培养的大鼠肾细胞中研究了雌激素受体-α（ERα）、雌激素受体相关受体-α（ERRα）与结石基质蛋白骨桥蛋白（OPN）之间的相互作用。成年雌性Wistar大鼠分为6组。第1组和第4组为正常雌性大鼠，第2组和第5组为去卵巢雌性大鼠，第3组和第6组为接受女性性激素补充的去卵巢雌性大鼠。第1 - 3组给予蒸馏水，而第4 - 6组给予0.5%乙二醇（EG）。此外，在各种条件下用女性性激素处理后，对大鼠肾原代培养细胞进行了检测。使用实时PCR检测全肾和原代培养细胞中ERα、ERRα和OPN - mRNA的表达。去卵巢抑制了OPN和ERRα - mRNA的表达。补充女性性激素增加了OPN和ERRα - mRNA的表达。相反，去卵巢增加了ERα - mRNA的表达，而补充女性性激素则抑制了其表达。原代培养细胞中的mRNA表达结果与高草酸尿模型大鼠中的结果一致。虽然ERα和ERRα - mRNA表达差异的原因尚不清楚，但雌激素可能通过ERα和/或ERRα独立或联合调节OPN的表达。此外，绝经后女性因雌激素去除导致的OPN减少可能会增加尿石症。
