A bstract. To examine the role of vitamin D in the renal tubular handling of calcium, clearance studies were performed in three groups of rats: group A rats fed a standard vitamin D-deficient diet (Ca 0.45%, P 0.3%) for 6 wk, were hypocalcemic with secondary hyperparathyroidism; group B rats fed the same diet as in group A but with high calcium (Ca 1.4%) and 20% lactose, were normocalcemic and without secondary hyperparathyroidism; group C rats fed the same diet as in group A but supplemented with 25 U of vitamin D3 orally twice a week, were normocalcemic, vitamin D-replete, and euparathyroid. After thyroparathyroidectomy (TPTX), each rat was infused intravenously with an electrolyte solution that contained a fixed concentration of calcium (0-30 mM) with or without parathyroid hormone (PTH; 0.75 or 2.5 U/h) at a rate of 3 ml/h. Urinary calcium excretion and serum calcium concentrations were measured between 16 and 19 h of the infusion, and the apparent threshold of calcium excretion was determined.The threshold of calcium excretion was lower in vitamin D-deficient TPTX rats (groups A and B) than in vitamin D-replete TPTX rats (group C), and not different between group A and group B. Administration of PTH at a dose of 0.75 U/h increased the threshold of calcium excretion by -0.6 mM in group C, but did not alter the threshold either in group A or group B. Administration

Previous results have shown that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances the synthesis of phosphatidylserine (PS) and suppresses the synthesis of phosphatidylethanolamine (PE) in osteoblast-like rat osteogenic sarcoma UMR 106 cells [Matsumoto, Kawanobe, Morita & Ogata (1985) J. Biol. Chem. 260, 13704-13709]. In the present study, the effect of parathyroid hormone (PTH) on phospholipid metabolism is examined by using these cells. Treatment of UMR 106 cells with human PTH-(1-34)-peptide suppresses the synthesis of phosphatidylethanolamine in a dose- and time-dependent manner without affecting the synthesis of PS. The maximal effect on PE synthesis is obtained with 2.4 nM-human PTH-(1-34)-peptide when the cells are treated for 48 h or longer. In addition, when human PTH-(1-34)-peptide is added together with the maximal dose of 1,25(OH)2D3, there is a further decline in PE synthesis, whereas the stimulation of PS synthesis by 1,25(OH)2D3 is not altered. Because methylation of PE is suggested to affect hormone receptor-adenylate cyclase coupling, the observed change in PE metabolism by PTH and 1,25(OH)2D3 may be, at least in part, involved in the development of desensitization phenomenon to PTH in these cells.

No abstract

No abstract

To evaluate the role of insulin in the regulation of circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] levels, serum 1,25(OH)2D concentrations in response to phosphorus (P) deprivation were examined in control, streptozotocin-diabetic and insulin-treated diabetic rats. Dietary P deprivation for 1 week caused a marked increase in serum 1,25(OH)2D level from 75 +/- 4 pg/ml to 274 +/- 16 pg/ml in control rats. In contrast, serum 1,25(OH)2D level was significantly lower in diabetic rats on a normal P diet (20 +/- 2 pg/ml) compared to that in control rats and increased only slightly by P deprivation (33 +/- 4 pg/ml). Treatment of the diabetic rats on normal P diet with insulin caused an increase in serum 1,25(OH)2D concentration to a level (82 +/- 10 pg/ml) similar to that in control rats and restored the increase in serum 1,25(OH)2D concentration in response to P deprivation (315 +/- 38 pg/ml). Although there was a marked decrease in serum phosphate level by P deprivation in all groups of animals, the rise in serum calcium level by P deprivation seen in control rats was abolished in diabetic rats. In addition, while bone mineral contents decreased significantly in response to P deprivation in control rats, no significant changes in either bone calcium or P contents were observed after P deprivation in diabetic rats. Insulin treatment of the diabetic rats recovered the responsiveness to P deprivation in both serum calcium level and bone mineral contents. P deprivation did not affect plasma glucose or serum creatinine level in any group of rats. These results suggest that insulin, either directly or indirectly, is required for the increase in circulating 1,25(OH)2D concentrations in response to P deprivation, and that the rise in serum 1,25(OH)2D level may play a role in the hypercalcemic response to P deprivation.