Growth hormone normalizes renal 1,25-dihydroxyvitamin D-3-24-hydroxylase gene expression but not Na+-phosphate cotransporter (Npt2) mRNA in phosphate-deprived Hyp mice

The murine X-linked Hyp mutation is characterized by decreased renal expression of type II Na+-phosphate (Pi) cotransporter (Npt2) mRNA and an abnormal vitamin D response to Pi deprivation, The latter is manifest by an aberrant fall in serum 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D) levels that is associated with an increase in renal 1,25(OH)(2)D-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway, Because growth hormone (GH) enhances renal Na+-Pi cotransport and permits the adaptive 1,25(OH)(2)D response in Pi-deprived hypophysectomized rats, we examined the effects of GH on vitamin D metabolism and renal Npt2 mRNA abundance in Hyp mice fed control and low Pi diets, GH significantly decreased renal 24-hydroxylase activity (0.202 +/- 0.020 to 0.098 +/- 0.008 pmol/mg of protein/minute, p < 0.05) and mRNA abundance, relative to beta-actin mRNA (299 +/- 13 to 78 +/- 14, p < 0.05), in Hyp, mice fed the low Pi diet but had no effect on either parameter in mutants fed the control diet. Moreover, after GH treatment, renal 24-hydroxylase gene expression was no longer elevated in Pi-deprived Hyp, mice relative to mutants fed control diet. In contrast, GH did not correct the serum concentration of 1,25(OH)(2)D in Pi-deprived Hyp mice, We also demonstrate that GH did not normalize renal Npt2 mRNA expression, relative to beta-actin mRNA, in Hyp mice fed either control or low Pi diets, The present data demonstrate that normalization of renal 24-hydroxylase gene expression in Pi-deprived Hyp, mice by GH is not sufficient to correct the serum concentration of 1,25(OH)(2)D and is not associated with an alteration in renal Npt2 mRNA expression.