Renal calcitriol synthesis and serum phosphorus in response to dietary phosphorus restriction and anabolic agents.
Calcitriol [1,25-(OH)2D3] synthesis by the renal 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase) is induced in rats on a low phosphorus diet, but not in the hypophysectomized (HPX) or diabetic rat. However, the normal response is restored by the administration of growth hormone (GH) or insulin-like growth factor-I (IGF-I), or insulin, respectively. To further characterize this in vivo phenomenon, the acute effects of GH, IGF-I, and insulin were studied in the HPX rat. In the HPX rat the low phosphorus diet alone did not significantly alter serum phosphorus or 1alpha-hydroxylase activity, but treatment with GH resulted in a marked decrease in serum phosphorus that was associated with a fivefold induction of enzyme activity. Time course studies showed that by 6 hours after GH administration, hepatic IGF-I mRNA had increased 10-fold while renal IGF-I mRNA had increased by only 52%. Between 6 and 12 hours, serum phosphorus decreased dramatically and 1alpha-hydroxylase activity increased twofold. Treatment of phosphorus-restricted HPX rats with IGF-I resulted in a decrease in serum phosphorus by 2 hours that preceded a fourfold increase in enzyme activity between 6 and 10 hours. Treatment of phosphorus-restricted HPX rats with insulin produced similar results. This is the first demonstration of hypophosphatemia preceding induction of the 1alpha-hydroxylase after administration of IGF-I or insulin to the HPX rat on a low phosphorus diet. Although these growth factors may have a direct effect on the 1alpha-hydroxylase, these data suggest that the influence of GH, IGF-I, and insulin on transcellular phosphorus flux may have an independent effect on enzyme activity. Furthermore, the much greater induction of hepatic compared with renal IGF-I mRNA in response to GH suggests that systemic, rather than the local, IGF-I may be required for induction of the 1alpha-hydroxylase. This effect may be mediated by either the insulin or the IGF-I receptor.
Grieff
M
M
Renal Division, Washington University School of Medicine, St. Louis, MO, USA.
Zhong
M
M
Finch
J
J
Ritter
C S
CS
Slatopolsky
E
E
Brown
A J
AJ
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis*; D004790:Enzyme Induction; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010758:Phosphorus / Q000097:blood*; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D016226:Phosphorus, Dietary; D010758:Phosphorus; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol