Insulin-like growth factor I regulates renal development in rodents.
Blocking the action of insulin-like growth factor I (IGF I) impairs kidney development in vitro. However, no renal developmental abnormalities have been reported in newborn transgenic mice that do not express IGF I (Igf1-/-) mice. Ninety-five percent of Igf1-/- mice die immediately following birth. Kidney development continues following birth in rodents. To readdress the question of the participation of IGF I in the process of kidney development, we measured nephron numbers in developed kidneys from Igf1-/- mice that survived past birth, and using a second model of kidney development, characterized the effect of IGF I infused into rat hosts on the renal function of transplanted metanephroi. Igf1-/- mice were born with grossly normal kidneys. At 77 +/- 10 days after birth, Igf1-/- mice that survived were approximately 28% the weight of wild-type (WT) littermates and had proportionally smaller kidneys. The number of nephrons per kidney was reduced by approximately 20% in Igf1-/- mice. Glomerular size was also reduced in Igf1-/- mice. In untreated host rats, neither the size nor inulin clearance of transplanted metanephroi changed significantly from 12-28 weeks postimplantation. The administration of IGF I to hosts did not affect the size of transplanted metanephroi measured at 12-16 weeks following implantation. However, inulin clearances were increased significantly by the administration of IGF I to hosts. Our findings 1) indicate that IGF I plays a role in determining nephron number, 2) suggest that it enhances function in developing kidneys, and 3) establish the potential for the pharmacological use of IGF I to enhance the growth and function of transplanted metanephroi.
D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development; D016030:Kidney Transplantation; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014185:Transplantation, Isogeneic