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成年单侧肾切除雄性大鼠肾小球AT1血管紧张素受体的生长激素调节

Growth hormone regulation of glomerular AT1 angiotensin receptors in adult uninephrectomized male rats.

作者信息

Mok Ka-Yin K, Sandberg Kathryn, Sweeny Joseph M, Zheng Wei, Lee Sunghou, Mulroney Susan E

机构信息

Department of Physiology and Biophysics, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057, USA.

出版信息

Am J Physiol Renal Physiol. 2003 Dec;285(6):F1085-91. doi: 10.1152/ajprenal.00383.2002. Epub 2003 Jun 24.

Abstract

Sex differences exist in the mechanisms initiating early compensatory renal growth after unilateral nephrectomy (UNX); remnant kidney growth is growth hormone (GH) independent in adult female rats and GH dependent in adult male rats. The present study determined whether sex differences also exist in angiotensin type 1 receptor (AT1R) regulation during early remnant kidney (REM) growth after UNX, and if so, whether GH modulates AT1R expression after UNX in the male rat. Scatchard analysis of radioligand binding in glomeruli demonstrated that 48 h post-UNX, AT1R density (Bmax) was significantly decreased by 20% in female REM compared with control kidneys. In contrast, male REM glomerular Bmax was significantly increased by 28% compared with control kidneys. Furthermore, GH-suppressed male rats displayed attenuated REM growth, which was associated with a 35% decrease in AT1R Bmax. Losartan treatment also decreased REM AT1R Bmax by 55%. The activity of mRNA binding proteins that bind to the 5' leader sequence of the AT1R was regulated by UNX and GH treatment in an inverse manner to AT1R expression. These findings suggest that in rats 1) there are sex differences in the regulation of glomerular AT1R expression after UNX; 2) the increase in AT1R binding sites in the male REM is regulated by GH and mediates early remnant kidney growth; and 3) AT1R 5' leader sequence mRNA binding proteins play a role in UNX and GH regulation of glomerular AT1Rs in both males and females.

摘要

单侧肾切除(UNX)后启动早期代偿性肾生长的机制存在性别差异;成年雌性大鼠的残余肾生长不依赖生长激素(GH),而成年雄性大鼠的残余肾生长依赖GH。本研究确定了UNX后早期残余肾(REM)生长过程中血管紧张素1型受体(AT1R)调节是否也存在性别差异,如果存在,GH是否在雄性大鼠UNX后调节AT1R表达。对肾小球放射性配体结合的Scatchard分析表明,UNX后48小时,与对照肾相比,雌性REM中的AT1R密度(Bmax)显著降低20%。相反,与对照肾相比,雄性REM肾小球Bmax显著增加28%。此外,GH抑制的雄性大鼠显示REM生长减弱,这与AT1R Bmax降低35%有关。氯沙坦治疗也使REM AT1R Bmax降低55%。与AT1R表达呈相反方式,结合于AT1R 5'前导序列的mRNA结合蛋白的活性受UNX和GH治疗调节。这些发现表明,在大鼠中:1)UNX后肾小球AT1R表达调节存在性别差异;2)雄性REM中AT1R结合位点的增加受GH调节并介导早期残余肾生长;3)AT1R 5'前导序列mRNA结合蛋白在雄性和雌性肾小球AT1R的UNX和GH调节中起作用。

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