Differential regulation of the bumetanide-sensitive cotransporter (NKCC2) by ovarian hormones

Differential regulation of the bumetanide-sensitive cotransporter (NKCC2) by ovarian hormones
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DOI:
10.1016/j.steroids.2010.05.014
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发表时间:
2010-11-01
期刊:
影响因子:
2.7
通讯作者:
Masilamani, Shyama M. E.
Masilamani, Shyama M. E.
中科院分区:
医学3区
文献类型:
--
作者:
Musselman, Teddy M.;Zhang, Zheng;Masilamani, Shyama M. E.

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Na-K-2Cl共转运体(NKCC2)调节钠沿Henle's袢厚升肢的转运,在控制钠平衡、肾浓缩能力和肾素释放中起重要作用。为了确定NKCC2的丰富度和/或分布是否存在性别差异,并评估卵巢激素对这种差异的贡献,我们对Sprague Dawley雄性、雌性和去卵巢(OVX)大鼠肾脏中的NKCC2进行了半定量免疫印迹和免疫过氧化物酶免疫组化,分别补充和不补充17- β雌二醇或黄体酮。与男性相比,完整女性在全肾(334 +/- 29%)、皮质(219 +/- 20%)和外髓质(133 +/- 9%)的匀浆中显示出更高的NKCC2蛋白。对OVX大鼠补充卵巢激素仅调节外髓质的NKCC2, NKCC2蛋白丰度在黄体酮的作用下略有下降,但在17- β雌二醇的作用下增加。免疫组化结果显示,厚升肢细胞的顶膜有明显的NKCC2标记。肾切片NKCC2标记证实了卵巢激素对NKCC2的区域化调控。随着性激素环境的变化,卵巢激素对NKCC2的局部调节可能对控制女性一生中钠和水的平衡具有重要意义。(C) 2010爱思唯尔公司版权所有。
The Na-K-2Cl cotransporter (NKCC2) regulates sodium transport along the thick ascending limb of Henle's loop and is important in control of sodium balance, renal concentrating ability and renin release. To determine if there are sex differences in NKCC2 abundance and/or distribution, and to evaluate the contribution of ovarian hormones to any such differences, we performed semiquantitative immunoblotting and immunoperoxidase immunohistochemistry for NKCC2 in the kidney of Sprague Dawley male, female and ovariectomized (OVX) rats with and without 17-beta estradiol or progesterone supplementation. Intact females demonstrated greater NKCC2 protein in homogenates of whole kidney (334 +/- 29%), cortex (219 +/- 20%) and outer medulla (133 +/- 9%) compared to males. Ovarian hormone supplementation to OVX rats regulated NKCC2 in the outer medulla only, with NKCC2 protein abundance decreasing slightly in response to progesterone but increasing in response to 17-beta estradiol. Immunohistochemistry demonstrated prominent NKCC2 labeling in the apical membrane of thick ascending limb cells. Kidney section NKCC2 labeling confirmed regionalized regulation of NKCC2 by ovarian hormones. Localized regulation of NKCC2 by ovarian hormones may have importance in controlling sodium and water balance over the lifetime of women as the milieu of sex hormones varies. (C) 2010 Elsevier Inc. All rights reserved.