Document Detail

Normal regulation of calcitriol production in Gy mice. Evidence for biochemical heterogeneity in the X-linked hypophosphatemic diseases.
MedLine Citation:
PMID:  2153705     Owner:  NLM     Status:  MEDLINE    
Phenotypic heterogeneity in X-linked hypophosphatemic rickets (XLH) is ascribed to variable penetrance of the genetic abnormality. However, studies of hypophosphatemic (Hyp) and gyrorotary (Gy) mice indicate that mutations at different loci along the X chromosome may underlie the genetically transmitted hypophosphatemic disorders. Thus, genetic heterogeneity may be a determinant of the phenotypic variability in XLH. To determine if such variance includes biochemical diversity, we examined whether Gy mice, similar to Hyp mice, exhibit abnormal regulation of renal 25-hydroxyvitamin D (25[OH]D)-1 alpha-hydroxylase. Serum phosphorus in Gy (4.7 +/- 0.3 mg/dl) and phosphate (P)-depleted mice (4.9 +/- 0.4) was significantly less than normal (8.4 +/- 0.5). Consistent with P depletion, the Gy mice exhibited enhanced renal 25(OH)D-1 alpha-hydroxylase activity (9.3 +/- 0.6 fmol/mg kidney per min), similar to that of P-depleted normals (9.1 +/- 1.5), but significantly greater than that of controls (3.1 +/- 0.3). Such normal enzyme responsiveness was confirmed upon PTH stimulation (1 IU/h s.c.), which revealed that Gy mice increased renal 1-hydroxylase (59 +/- 7.7) similarly to normals (65 +/- 7.7) and P-depleted animals (58.4 +/- 7.8). Calcitonin administration also enhanced enzyme function comparably in the animal models. Evidence confirming normally responsive calcitriol production in untreated Gy mice included increased serum 1,25-dihydroxyvitamin D levels, gastrointestinal calcium absorption, and urinary calcium. The normally regulated vitamin D metabolism in Gy mice indicates that biochemically diverse disease may result from mutations in the gene family regulating renal P transport and underlying X-linked hypophosphatemia. We suspect such heterogeneity is due to altered P transport at variable segments of the proximal convoluted tubule.
G A Davidai; T Nesbitt; M K Drezner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  85     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1990 Feb 
Date Detail:
Created Date:  1990-03-15     Completed Date:  1990-03-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  334-9     Citation Subset:  AIM; IM    
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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MeSH Terms
25-Hydroxyvitamin D3 1-alpha-Hydroxylase / analysis
Calcitriol / biosynthesis*
Calcium / metabolism
Hypophosphatemia, Familial / genetics*
Intestinal Absorption
Kidney / metabolism
Mice, Inbred C3H
Parathyroid Hormone / pharmacology
Phosphates / blood*
Vitamin D / metabolism
X Chromosome*
Grant Support
Reg. No./Substance:
0/Parathyroid Hormone; 0/Phosphates; 1406-16-2/Vitamin D; 32222-06-3/Calcitriol; 7440-70-2/Calcium; EC 1.14.-/25-Hydroxyvitamin D3 1-alpha-Hydroxylase

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