The growth hormone-insulin-like growth factor I axis and renal glomerular function.
This study examined whether maneuvers that chronically raise or lower serum insulin-like growth factor I (IGF-I), within physiological and pathophysiological ranges, will affect glomerular hemodynamics. Pair-fed Munich Wistar rats received, for 6 to 7 days, continuous s.c. infusions of human recombinant IGF-I (rhIGF-I; 125 micrograms/day), vehicle, or s.c. injection of a synthetic growth hormone-releasing hormone antagonist (GHRH-ANT) (N = 7 in each group). Infusion of rhIGF-I raised serum IGF-I to about 180% of control values, and GHRH-ANT injections lowered serum IGF-I to about 33% of control. The IGF-I infusion induced an increase in left kidney weight when expressed in absolute units but not when expressed as a percentage of body weight; there was also an increase in glomerular volume in the IGF-I treated rats. GFR, single nephron GFR, and single nephron plasma flow also rose with IGF-I infusion, and these changes were associated with decreased afferent and efferent arteriolar resistance and increased glomerular ultrafiltration coefficient. GHRH-ANT injection did not affect kidney weight or glomerular volume; however, GFR, single nephron GFR, and single nephron plasma flow were reduced in association with an increase in efferent arteriolar resistance. There also was a tendency, not significant, for the glomerular ultrafiltration coefficient to decrease. The findings that a low dose of rhIGF-I, which raised the serum IGF-I only modestly, increased glomerular ultrafiltration and that reducing serum IGF-I below control values decreased glomerular dynamics suggest that physiological or pathophysiological changes in IGF-I may affect and possible help to regulate glomerular function.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirschberg
R
R
Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance.
Kopple
J D
JD
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D013006:Growth Hormone / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D017337:Sermorelin
D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone