GROWTH-HORMONE NORMALIZES RENAL 1,25-DIHYDROXYVITAMIN D-3-24-HYDROXYLASE GENE-EXPRESSION BUT NOT NA-PHOSPHATE COTRANSPORTER (NPT2) MESSENGER-RNA IN PHOSPHATE-DEPRIVED HYP MICE()

The murine X-linked Hyp mutation is characterized by decreased renal e xpression of type II Na+-phosphate (Pi) cotransporter (Npt2) mRNA and an abnormal vitamin D response to Pi deprivation, The latter is manife st 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 hypophy sectomized rats, we examined the effects of GH on vitamin D metabolism and renal Npt2 mRNA abundance in Hyp mice fed control and low Pi diet s, 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 mRN A 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 p arameter in mutants fed the control diet. Moreover, after GH treatment , renal 24-hydroxylase gene expression was no longer elevated in Pi-de prived 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-deprive d Hyp mice, We also demonstrate that GH did not normalize renal Npt2 m RNA expression, relative to beta-actin mRNA, in Hyp mice fed either co ntrol or low Pi diets, The present data demonstrate that normalization of renal 24-hydroxylase gene expression in Pi-deprived Hyp, mice by G H 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 expressio n.