Insulin-like growth factor I increases renal 1, 25(OH)₂D₃biosynthesis during low-P diet in adult rats

Dietary P restriction increases renal 1, 25-dihydroxyvitamin D3[1, 25(OH)2Ds] biosynthesis through stimulation of proximal tubule 25-hydroxyvitamin D3-lahydroxylase (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-I 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 protein1-5 mUr1, 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-day"1) for 72 h increased 1-OHase (65.2 ±5.88 vs. 95.1 ±7.26 pg-mg proteinru5 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.