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1 Departments of Physiology & Biophysics, Georgetown University, Wash, DC, USA
2 Department of Medicine, Georgetown University, Wash, DC, USA; Departments of Physiology & Biophysics, Georgetown University, Wash, DC, USA
3 Department of Medicine, Georgetown University, Wash, DC, USA
* To whom correspondence should be addressed. E-mail: mulrones{at}georgetown.edu.
Sex differences exist in the mechanisms initiating early compensatory renal growth following 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 if sex differences also exist in angiotensin type 1 receptor (AT1R) regulation during early remnant kidney (REM) growth following UNX, and if so, whether GH modulates AT1R expression following UNX in the male rat. Scatchard analysis of radioligand binding in glomeruli demonstrated that 48 h post-UNX, AT1R Bmax was significantly decreased by 20% in female REM compared with control kidneys. In contrast, male REM glomerular AT1R 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 finding suggest that in rats: 1) there are sex differences in the regulation of glomerular AT1R expression following 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'LS mRNA binding proteins play a role in UNX- and GH-regulation of glomerular AT1Rs in both males and females.
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