Insulin-like growth factor I increases renal 1,25(OH)2D3 biosynthesis during low-P diet in adult rats.
Dietary P restriction increases renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] biosynthesis through stimulation of proximal tubule 25-hydroxyvitamin D3-1 alpha-hydroxylase (1-OHase). Because insulin-like growth factor I (IGF-I) is required for 1-OHase stimulation by low-P diet (LPD) and because 1-OHase stimulation by low-Ca diet and parathyroid hormone is lost with aging, studies were undertaken to determine whether 1-OHase activity during LPD is impaired with age and whether IGF-1 can increase 1-OHase activity in adult rats. Five days of LPD increased in vitro 1-OHase activity in young (97.3 +/- 13.5 vs. 49.7 +/- 6.8 pg.mg protein-1.5 min-1, P < 0.005) but not adult (42.3 +/- 5.37 vs. 41.2 +/- 8.9) rats. In LPD-fed adult rats, recombinant human IGF-I (rhIGF-I, 1.4 mg.kg body wt-1.day-1) for 72 h increased 1-OHase (65.2 +/- 5.88 vs. 95.1 +/- 7.26 pg.mg protein-1.5 min-1, P < 0.005). The results show that the rise in 1-OHase activity during LPD is lost in adult rats and that rhIGF-I can overcome the inhibition and stimulate renal 1-OHase activity to levels observed in young animals. The studies indicate that the age-related loss of 1-OHase activity is reversible.
Wong
M S
MS
Section of Endocrinology, University of Chicago Pritzker School of Medicine, Illinois 60637, USA.
Sriussadaporn
S
S
Tembe
V A
VA
Favus
M J
MJ
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010758:Phosphorus / Q000097:blood; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D016226:Phosphorus, Dietary; D011994:Recombinant Proteins; D010758:Phosphorus; D007334:Insulin-Like Growth Factor I; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol