The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels.
A sensitive radioreceptor assay for 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five-fold increase in the plasma level of 1alpha,25-(OH)2D3. The enhancement of 1alpha,25-(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect. In contrast, the response to phosphate deficiency is independent of these glands and may result from a direct action of low phosphate on the renal synthesis of 1alpha,25-(OH)2D3. Studies in humans indicate that the normal level of 1alpha,25-(OH)2D is 2.1--4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1alpha,25-(OH)2D and this kidney hormone is undetectable in anephric subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparathyroidism are associated with reduced plasma 1alpha,25-(OH)2D while patients with primary hyperparathyroidism have significantly elevated sterol hormone levels. Thus, from measurements in rats and humans, it appears that circulating 1alpha,25-(OH)2D3 is regulated by PTH and/or phosphate and that abnormal plasma 1alpha,25-(OH)2D3 is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders.
D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D002645:Chickens; D004032:Diet; D004100:Dihydroxycholecalciferols / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010710:Phosphates / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D012279:Rickets / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology; D013965:Thyroidectomy; D014184:Transplantation, Homologous
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010710:Phosphates; D011956:Receptors, Cell Surface; D002118:Calcium