title: Growth hormone normalizes renal 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression but not Na+-phosphate cotransporter (Npt2) mRNA in phosphate-deprived Hyp mice.
abstract: 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 D3 (1,25(OH)2D) levels that is associated with an increase in renal 1,25(OH)2D-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)2D 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)2D 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)2D and is not associated with an alteration in renal Npt2 mRNA expression.
authors.affiliation: McGill University-Montreal Children's Hospital Research Institute, Department of Pediatrics, McGill University, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: J
authors.initials: J
authors.lastname: Martel
authors.forename: H S
authors.initials: HS
authors.lastname: Tenenhouse
mesh_terms: D000821:Animal Feed; D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D013006:Growth Hormone / Q000494:pharmacology*; D007015:Hypophosphatemia, Familial / Q000235:genetics*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000201:enzymology; D010710:Phosphates / Q000097:blood / Q000172:deficiency; D010716:Phosphatidylinositols / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D013250:Steroid Hydroxylases / Q000235:genetics*; D027981:Symporters; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D002352:Carrier Proteins; D010710:Phosphates; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C493549:Slc17a2 protein, mouse; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol