THE ASSAY OF 1α, 25‐DIHYDROXYVITAMIN D3: PHYSIOLOGIC AND PATHOLOGIC MODULATION OF CIRCULATING HORMONE LEVELS

Abstract

A sensitive radioreceptor assay for 1α,25-dihydroxyvitamin D₃ (1α,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 1α,25-(OH)₂D₃. The enhancement of 1α,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 1α,25-(OH)₂D₃. Studies in humans indicate that the normal level of 1α,25-(OH)₂D is 2.1-4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1α,25-(OH)₂D and this kidney hormone is undectectable in anephirc subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparatghyroidism are associated with reduced plasma 1α,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 1α,25-(OH)₂D₃ is regulated by PTH and/or phosphate and that abnormal plasma 1α,25-(OH)₂D₃ is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders.