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

Departments of ¹Physiology and Biophysics and ²Medicine, Georgetown University School of Medicine, Washington, District of Columbia 20007

Submitted 24 October 2002 ; accepted in final form 21 June 2003

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 (B_max) was significantly decreased by 20% in female REM compared with control kidneys. In contrast, male REM glomerular B_max 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 B_max. Losartan treatment also decreased REM AT₁R B_max 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.

renin-angiotensin system; renal mass ablation; mRNA binding proteins; sexual dimorphism

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