title: Decreased concentration of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with X-linked hypophosphatemic rickets: effect of phosphate supplementation.
abstract: Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets (XLH). However, the resistance to vitamin D treatment in XLH cannot be explained by hypophosphatemia alone. Since most of the actions of vitamin D are mediated by its receptors (VDR), abnormalities of VDR have been postulated in XLH. In order to investigate this possibility, we measured the concentration of VDR in PHA-activated peripheral mononuclear cells from 10 XLH patients. Patients without phosphate supplementation showed significantly lower concentration (21.7 +/- 5.1 fmol/mg protein, mean +/- SEM) compared to the normal controls (60.7 +/- 4.0). On the contrary, there was no significant difference between the phosphate-supplemented patients (58.3 +/- 2.7) and controls. There was a significant positive correlation between VDR concentration and serum phosphate (P less than 0.05). In two patients, VDR was increased after daily phosphate supplementation was started. These results indicate that a decreased concentration of VDR secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH.
authors.affiliation: Department of Pediatrics, Osaka University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000097:blood* / Q000627:therapeutic use; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D012279:Rickets / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D014960:X Chromosome
chemical_list: D010710:Phosphates; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid