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.

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http://dx.doi.org/10.1016/s0272-6386(96)90472-2DOI Listing

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