Dietary phosphorus deprivation induces 25-hydroxyvitamin D₃ 1α-hydroxylase gene expression

Dietary phosphorus deprivation causes hypophosphatemia and an increase in serum 1α,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] concentrations. To determine the molecular mechanisms of this regulation, the effects of dietary phosphorus deprivation and hypophysectomy on 25-hydroxyvitamin D₃ 1α-hydroxylase (1_a-hydroxylase) protein and messenger RNA (mRNA) expression were examined in rats. A low phosphorus diet (LPD) for 4 days resulted in hypophosphatemia and an increase in serum 1,25-(OH)₂D₃ levels. This increase was caused by the induction of 1α-hydroxylase protein and mRNA expression (4- and 10-fold increases, respectively). Administration of the LPD or normal phosphorus diet to hypophysectomized (HPX) rats resulted in hypophosphatemia and suppression of 1α-hydroxylase gene expression, indicating that hypophosphatemia itself is not sufficient to induce 1α-hydroxylase mRNA expression. Administration of GH to HPX rats fed LPD could partially restore 1α-hydroxylase mRNA expression, whereas supplementation with insulin-like growth factor I, T₃, estrogen, or corticosterone had no effect. We also examined Phex gene expression in the bone, because the clinical features of X-linked hypophosphatemia resemble those of HPX rats. Phex mRNA expression, however, was not altered in HPX rats. In conclusion, we demonstrated that the increase in serum 1,25-(OH)₂D₃ levels caused by dietary phosphorus deprivation is due to the induction of 1α-hydroxylase mRNA expression, and this increase is mediated in part by a GH-dependent mechanism.