Growth hormone regulation of glomerular AT₁angiotensin receptors in adult uninephrectomized male rats

Abstract

roney. Growth hormone regulation of glomerular AT1 angiotensin receptors in adult uninephrectomized male rats. Am J Physiol Renal Physiol 285: F1085-F1091, 2003. First published June 24, 2003 10.1152/ajprenal.00383.2002.-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 5Ј 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 5Ј leader sequence mRNA binding proteins play a role in UNX and GH regulation of glomerular AT 1Rs in both males and females.

Posttranscriptional mechanisms contribute to osmotic regulation of ANG type 1 receptors in cultured rat renomedullary interstitial cells

“…These findings are consistent with our previous studies that showed RNA-protein complex formation in the AT 1a R 5ЈLS is regulated in a manner that inversely correlates with changes in AT 1 R densities under a variety of conditions, including dietary sodium manipulation (16), estrogen deficiency (33), and renal mass ablation (22).…”

“…Under these experimental conditions, there were no significant differences in the degree of receptor internalization in RMICs cultured under isoosmotic or hyperosmotic conditions [endocytosis rate constant (min Effect of osmolality on AT 1 R RNA-protein complex formation in RMICs. We have previously shown that alterations in the levels of cytosolic proteins, which bind to the 5ЈLS of the AT 1a R are associated with inverse changes in AT 1a R protein expression (15,16,22). To determine whether osmolality alters the levels of RNA-protein complex (RPC) formation in the 5ЈLS in RMICs, we performed RNA EMSAs with radiolabeled 5ЈLS on cytosolic extracts prepared from RMICs cultured under isoosmotic and hyperosmotic conditions (Fig.…”

Sex differences in the developmental origins of hypertension and cardiorenal disease

“…Alternatively, recent work implicates growth hormone (GH) in sex-dependent differences in renal expression of glomerular AT 1 during hypertrophy following uninephrectomy; male rat kidneys show increased glomerular AT 1 expression, whereas females do not (86). Because there is sexual dimorphism in GH release these observations may hold implications for both normal and pathological growth and development of the kidney.…”

Sex Differences in the Developmental Programming of Adult Disease

“…Taken together, it appears that the influence of sex on the developmental origins of disease may reach far beyond the widely recognized role of sex hormones. Alternatively, recent work implicates growth hormone (GH) in sex dependent differences in renal expression of glomerular AT 1 during hypertrophy following uninephrectomy; male rat kidneys show increased glomerular AT 1 expression, whereas females do not (Mok et al, 2003). Because there is sexual dimorphism in GH release these observations may hold implications for both normal and pathological growth and development of the kidney.…”