Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition
Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition
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DOI：
10.1152/ajprenal.00029.2004
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发表时间：
2004-07-01
影响因子：
4.2
通讯作者：
Sabolic, I
中科院分区：
文献类型：
--
作者：
Ljubojevic, M;Herak-Kramberger, CM;Sabolic, I
在大鼠中，雄性 (M) 肾脏分泌的对氨基马尿酸 (PAH) 高于雌性 (F)。主要肾脏 PAH 转运蛋白 OAT1 和 OAT3 在这些性别差异的产生中的作用以及负责的激素和机制尚未阐明。在这里，我们使用各种免疫细胞化学方法来研究性别、性腺切除术和性激素治疗对 OAT1 和 OAT3 沿大鼠肾单位的定位和丰度的影响。两种转运蛋白均定位于基底外侧膜：OAT1 在近端小管 S2 段中较强，在 S3 段中较弱，而 OAT3 在近端小管 S1 和 S2 段、粗升肢、远端小管以及沿集合管的主细胞中染色。成年大鼠两种转运蛋白表达的性别差异（M > F）仅在皮质小管中观察到。成年 M 中的皮质中的 OAT1 因去势而强烈减少，而用睾酮、雌二醇或黄体酮治疗去势后的 M 分别导致其完全恢复、进一步抑制或部分恢复。在成人F中，卵巢切除术后OAT1的表达微弱增加，而雌二醇治疗卵巢切除F的OAT1表达强烈下降。 OAT3在M和F皮质中的表达基本上遵循相似的模式，除了卵巢切除和黄体酮治疗没有显示出效果，而在其他组织区域中没有观察到性别差异。在青春期前的大鼠中，肾皮质中OAT1和OAT3的表达较低，并且没有表现出性别差异。我们的数据表明，大鼠肾皮质 OAT1 和 OAT3 (M > F) 的性别差异出现在青春期后，并且由雄激素（对于 OAT1 为孕激素）的刺激作用和雌激素的抑制作用决定。
In rats, the secretion of p-aminohippurate (PAH) by the kidney is higher in males ( M) than in females ( F). The role of the major renal PAH transporters, OAT1 and OAT3, in the generation of these gender differences, as well as the responsible hormones and mechanisms, has not been clarified. Here we used various immunocytochemical methods to study effects of gender, gonadectomy, and treatment with sex hormones on localization and abundance of OAT1 and OAT3 along the rat nephron. Both transporters were localized to the basolateral membrane: OAT1 was strong in proximal tubule S2 and weak in the S3 segments, whereas OAT3 was stained in proximal tubule S1 and S2 segments, thick ascending limb, distal tubule, and in principal cells along the collecting duct. Gender differences in the expression of both transporters in adult rats (M > F) were observed only in the cortical tubules. OAT1 in the cortex was strongly reduced by castration in adult M, whereas the treatment of castrated M with testosterone, estradiol, or progesterone resulted in its complete restitution, further depression, or partial restitution, respectively. In adult F, ovariectomy weakly increased, whereas estradiol treatment of ovariectomized F strongly decreased, the expression of OAT1. The expression of OAT3 in the M and F cortex largely followed a similar pattern, except that ovariectomy and progesterone treatment showed no effect, whereas in other tissue zones gender differences were not observed. In prepubertal rats, the expression of OAT1 and OAT3 in the kidney cortex was low and showed no gender differences. Our data indicate that gender differences in the rat renal cortical OAT1 and OAT3 (M > F) appear after puberty and are determined by both a stimulatory effect of androgens ( and progesterone in the case of OAT1) and an inhibitory effect of estrogens.