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-hydroxylase activity (1-OHase) during dietary calcium restriction is mediated by an increase in parathyroid hormone (PTH) and is inhibited by aging. Recent studies in mature (3-4 mo) rats demonstrated that insulin-like growth factor-I (IGF-I) restored stimulation of renal 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] production by low phosphorus diet (LPD), another major stimulus of 1-OHase. These studies were designed to determine whether IGF-I stimulates 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, 0.2 g Ca/kg diet) for 14 d, and recombinant human IGF-I [rhIGF-I, 1.4 mg/(24h 160 kg body wt)] or vehicle was administrated via miniosmotic pump for 72 h before killing. In 4-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. LCD increased in vitro1-OHase activity in young (1-mo-old) but not old (24-mo-old) male Fischer 344 rats. RhIGF-I increased 1-OHase activity in 24 mo-old rats fed LCD to levels that were not different from those in 1-mo-old rats fed LCD. The results indicate that the adaptive increase in 1-OHase activity due to a LCD is lost by 4 mo in rats and can be restored by pharmacologic doses of rhIGF-I.
Wong
M S
MS
The Open Laboratory of Asymmetric Synthesis, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Kowloon, Hong Kong, PRC.
Tembe
V A
VA
Favus
M J
MJ
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002117:Calcitriol / Q000096:biosynthesis* / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol