Growth hormone regulation of glomerular AT1 angiotensin receptors in adult uninephrectomized male rats.
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.
Mok
Ka-Yin K
KY
Department of Physiology and Biophysics, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Sandberg
Kathryn
K
Sweeny
Joseph M
JM
Zheng
Wei
W
Lee
Sunghou
S
Mulroney
Susan E
SE
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000254:growth & development / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D017978:Receptors, Growth Factor; D013006:Growth Hormone; D019808:Losartan