Role of 1,25-dihydroxyvitamin D on the skeletal resistance to parathyroid hormone.
Hypocalcemia in chronic renal failure (CRF) has been attributed in part to a skeletal resistance (S.R.) to the calcemic action of parathyroid hormone (PTH) as a consequence of low levels of 1,25(OH)2D3. To further elucidate the role of 1,25(OH)2D3 in the genesis of S.R., the calcemic effect of infusion of synthetic b-PTH 1-34 was examined in dogs before and after 7, 90 and 180 days of CRF. The maximum increment in ionized calcium after the infusion of PTH in the normal dogs was 1.15 +/- 0.13 mg/dl, decreased to 0.84 +/- 0.09 after 7 days, 0.68 +/- 0.1 after 90 days and to 0.66 +/- 0.11 mg/dl after 180 days of CRF. Thereafter, the dogs received 1,25(OH)2D3, 0.5 microgram daily for seven days and the studies were repeated. No improvement in the calcemic response to PTH was observed (0.57 +/- 0.26 mg/100 ml). Subsequently, a parathyroidectomy (PTX) was performed and 24 hours later the studies were repeated. After the infusion of PTH the calcemic response returned to normal (0.93 +/- 0.14 mg/dl). Further studies were performed in a group of four uremic dogs receiving no 1,25(OH)2D3, in which a PTX was performed 24 hours prior to the infusion of PTH. For this group, the increase in serum ionized calcium was 0.99 +/- 0.11 mg/dl. These values were not statistically different from normal dogs. In summary: (1) renal insufficiency was characterized by an abnormal calcemic response to PTH; (2) the administration of 1,25(OH)2D3 did not correct the S.R. to PTH; and (3) PTX performed 24 hours before the infusion of PTH restored the calcemic response to normal. These data suggest that high levels of endogenous parathyroid hormone desensitized the skeleton to the administration of exogenous PTH. These studies indicate that low values of 1,25(OH)2D3 are not directly responsible for the skeletal resistance to PTH in chronic renal failure.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
T
T
Galceran
K J
KJ
Martin
J J
JJ
Morrissey
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E
Slatopolsky
D000818:Animals; D001842:Bone and Bones / Q000503:physiopathology*; D002117:Calcitriol / Q000502:physiology; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D004285:Dogs; D005260:Female; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D010280:Parathyroid Glands / Q000502:physiology / Q000601:surgery; D010281:Parathyroid Hormone / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D010758:Phosphorus / Q000378:metabolism
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine; D010758:Phosphorus; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium