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Vitamin D metabolites and growth hormone therapy in uraemic rats: the short-term effect on growth failure and hyperparathyroidism
Authors:Satosi  HISANO   Craig B  LANGMAN   Kay  LATTA   Richard J  KRIEG JR James CM  CHAN
Affiliation:Department of Pediatrics, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia, United States of America;Children's Memorial Hospital, Northwestern University, Chicago, Illinois, United States of America;Department of Anatomy, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia, United States of America
Abstract:Summary: The aim of our study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (D), 22-oxacalcitriol (O) or recombinant human growth hormone (GH) on growth failure and hyperparathyroidism in 5/6 nephrectomized uraemic (Ur) rats. Seven groups of rats were studied: (i) sham controls (SC; n =6); (ii) Ur controls (UrC; n =8); (iii) Ur treated either with D (UrD; n =7); (iv) O (UrO, n =8); (v) GH (UrGH; n =7); (vi) D+GH (UrDGH; n =9); or (vii) O+GH (UrOGH; n =7). For 14 days, D and O were administered intraperitoneally daily at 30 ng/kg per day and GH subcutaneously daily at 1.3 i.u./day. Four weeks after 5/6 nephrectomy, plasma creatinine (Cr), plasma and urine calcium (Ca), plasma phosphate (P), ratio of urine Ca/urine Cr, amino-terminal parathyroid hormone (PTH; pg/mL) and Ca/dry bone weight in the left femur (mg/g) were measured. Uraemic controls, UrD, UrO and UrDGH rats were lower in weight gain than SC rats over the study period, but linear growth was not retarded in any uraemic group. Plasma Cr was greatly increased in any Ur group as compared with SC group. Plasma Ca and P concentrations did not differ among each group. the ratio of urine Ca/urine Cr in UrD and UrDGH groups was higher than SC, UrCand UrGH groups. the use of Dor D+GH suppressed PTH, returning the level in these rats to the normal level of the SC rats, while the PTH concentrations in the UrO and UrOGH rats were less decreased. Bone Ca content was enhanced by D+GH and O+GH administration in comparison with UrC rats, but there was no difference in the bone Ca content between UrD and UrDGH rats, and between UrO and UrOGH rats. In conclusion, growth failure in weight was shown in uraemia, but linear growth was not retarded in any uraemic group. 1.25 dihydroxyvitamin D3 and D plus GH successfully suppressed secondary hyperparathyroidism. Further studies are needed in order to elucidate the interactions on bone between vitamin D rnctabolites and GH.
Keywords:1,25 dihydroxyvitamin D3    22-oxacalcitriol    growth hormone    growth retardation    hyper parathyroidism    uraemia
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