INSULIN-LIKE-GROWTH-FACTOR-I INCREASES RENAL 1,25(OH)(2)D-3 BIOSYNTHESIS DURING LOW-P DIET IN ADULT-RATS

Dietary P restriction increases renal 1,25-dihydroxyvitamin D-3 [1,25( OH)(2)D-3] biosynthesis through stimulation of proximal tubule 25-hydr oxyvitamin D-2-1 alpha-hydroxylase (1-OHase). Because insulin-like gro wth 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 wheth er 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 increase d 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 (r hIGF-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 stimula te renal 1-OHase activity to levels observed in young animals. The stu dies indicate that the age-related loss of 1-OHase activity is reversi ble.