4.5 Article

Growth hormone regulation of glomerular AT(1) angiotensin receptors in adult uninephrectomized male rats

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 285, Issue 6, Pages F1085-F1091

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00383.2002

Keywords

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

Funding

  1. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL057502] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE ON AGING [R01AG019291] Funding Source: NIH RePORTER
  3. NHLBI NIH HHS [R01 HL 57502] Funding Source: Medline
  4. NIA NIH HHS [AG 19291] Funding Source: Medline

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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 (AT(1)R) regulation during early remnant kidney ( REM) growth after UNX, and if so, whether GH modulates AT(1)R expression after UNX in the male rat. Scatchard analysis of radioligand binding in glomeruli demonstrated that 48 h post-UNX, AT(1)R density (B-max) 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 AT(1)R B-max. Losartan treatment also decreased REM AT(1)R B-max by 55%. The activity of mRNA binding proteins that bind to the 5' leader sequence of the AT(1)R was regulated by UNX and GH treatment in an inverse manner to AT(1)R expression. These findings suggest that in rats 1) there are sex differences in the regulation of glomerular AT(1)R expression after UNX; 2) the increase in AT(1)R binding sites in the male REM is regulated by GH and mediates early remnant kidney growth; and 3) AT(1)R 5' leader sequence mRNA binding proteins play a role in UNX and GH regulation of glomerular AT(1)Rs in both males and females.

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