Insulin-like growth factor-I stimulates renal 1,25-dihydroxycholecalciferol synthesis in old rats fed a low calcium diet

The adaptive increase in renal proximal tubule 25-hydroxyvitamin D-alpha-hy droxylase activity (1-OHase) during dietary calcium restriction is mediated by an increase in parathyroid hormone (PTH) and is inhibited by aging. Rec ent studies in mature (3-4 mo) rats demonstrated that insulin-like growth f actor-I (IGF-I) restored stimulation of renal 1,25-dihydroxycholecalciferol [1,25(OH)(2)D-3] production by low phosphorus diet (LPD), another major st imulus of 1-OHase. These studies were designed to determine whether IGF-I s timulates 1-OHase during low calcium intake in old rats. Male rats were fed a normal calcium diet (NCD, 6 g Ca/kg diet) or low calcium diet (LCD, 0.2g Ca/kg diet) for 14 d, and recombinant human IGF-I [rhIGF-I, 1.4 mg/(24h 16 0 kg body wt)] or vehicle was administrated via miniosmotic pump for 72 h b efore killing. In I-mo-old male Sprague-Dawley rats,LCD increased in vitro renal 1-OHase activity in the presence but not in the absence of rhIGF-I. L CD increased in vitro1-OHase activity in young (1-mo-old) but not old (24-m o-old) male Fischer 344 rats, RhIGF-I increased 1-OHase activity in 24 mo-o ld rats fed LCD to levels that were not different from those in I-mo-old ra ts fed LCD. The results indicate that the adaptive increase in 1-OHase acti vity due to a LCD is lost by 4 mo in rats and can be restored by pharmacolo gic doses of rhIGF-I.