Effect of aging on the metabolism of phosphorus and 1,25-dihydroxyvitamin D in healthy men

1996 ◽  
Vol 270 (3) ◽  
pp. E483-E490
Author(s):  
A. A. Portale ◽  
B. P. Halloran ◽  
R. C. Morris ◽  
E. T. Lonergan
Keyword(s):  
Time Course ◽  
Young Men ◽  
Normal Serum ◽  
Serum Phosphorus ◽  
Serum Concentrations ◽  
Elderly Men ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Healthy Elderly ◽  
Dietary Phosphorus

We tested the hypothesis that aging alters physiological regulation of the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] by inorganic phosphorus. In seven elderly men [age 71 +/- 1 (SE) yr] and 9 young men (29 +/- 2 yr), dietary phosphorus was first normal, then increased and decreased within its normal range. At each intake of phosphorus, serum concentrations of 1,25(OH)2D in the elderly did not differ from those in young men, but fasting and 24-h mean serum concentrations of phosphorus were lower in elderly men. With phosphorus restriction, in each group serum 1,25(OH)2D increased by 47%, and 24-h mean serum phosphorus decreased by 0.6 +/- 0.1 mg/dl. Serum concentrations of 1,25(OH)2D varied inversely with 24-h mean serum phosphorus (R= -0.92, P<0.0001). Thus, in healthy elderly men in whom glomerular filtration rate is normal or near normal, serum concentrations of 1,25(OH)2D increase when dietary phosphorus is restricted; the magnitude of response at steady state is unaffected by aging, but the time course of response is delayed. At any level of serum phosphorus, serum 1,25(OH)2D is lower than that in young men, as reflected by a lower intercept of regression of serum 1,25(OH)2D on 24-h mean phosphorus.

Effects of acute and chronic treatment with glucocorticoids on the intestinal absorption of calcium and phosphate and on plasma 1,25-dihydroxyvitamin D levels in pigs

1985 ◽  
Vol 69 (5) ◽  
pp. 553-559 ◽  
Author(s):  
John Fox ◽  
Richardus Ross ◽  
Anthony D. Care
Keyword(s):  
Intestinal Absorption ◽  
Plasma Levels ◽  
Time Course ◽  
Chronic Treatment ◽  
Intestinal Loop ◽  
Phosphate Absorption ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Young Pigs ◽  
Proximal Small Intestine

1. We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids. 2. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or betamethasone was without effect on the absorption of calcium or phosphate. 3. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15–20% for 2–3 days before the trend was reversed and absorption was progressively reduced. 4. Chronic treatment with betamethasone inhibited only the active component of calcium and phosphate absorption. 5. Treatment with betamethasone was associated with a sustained 25–50% increase, to a maximum by 2 days, in the absorption of sodium, glucose and water. 6. Plasma levels of 1,25-dihydroxyvitamin D were reduced within 2 days of the start of treatment and reached a minimum (40–50% decrease) in 4–6 days. 7. We conclude that the initial stimulation of calcium and phosphate absorption is caused by the increased absorption of water. The long-term decrease in absorption may not be caused solely by the decreased circulating levels of 1,25-dihydroxyvitamin D since absorption continued to fall for several weeks after 1,25-dihydroxyvitamin D levels had reached a minimum.

Regulation of 1,25 (OH)2D synthesis in hypoparathyroidism and pseudohypoparathyroidism

1988 ◽  
Vol 255 (5) ◽  
pp. E730-E736
Author(s):  
N. A. Breslau ◽  
R. S. Weinstock
Keyword(s):  
Serum Phosphorus ◽  
Phosphorus Concentration ◽  
Parathyroid Hormone Receptor ◽  
Cyclic Monophosphate ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Complex Patients ◽  
Phosphorus Deprivation ◽  
Parathyroid Extract ◽  
Phosphorus Levels

We examined the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] synthesis in patients with hypoparathyroidism (n = 5) and pseudohypoparathyroidism (n = 5) by administration of parathyroid extract (PTE) and N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and by phosphorus deprivation with antacids. In response to PTE, patients with hypoparathyroidism increased serum 1,25(OH)2D from 17 +/- 5 to 30 +/- 5 (SD) pg/ml (P less than 0.01). An approximate doubling of the 1,25(OH)2D concentration also occurred following dbcAMP infusion or phosphorus deprivation (serum phosphorus 4.4 +/- 0.5 to 2.6 +/- 1.1, P less than 0.01). Serum phosphorus and 1,25(OH)2D concentrations were inversely correlated (r = -0.73, P less than 0.001). Patients with pseudohypoparathyroidism had negligible responses to PTE with respect to urinary adenosine 3', 5'-cyclic monophosphate excretion, serum phosphorus concentration, or 1,25(OH)2D synthesis. They did show a rise in serum 1,25(OH)2D from 17 +/- 4 to 44 +/- 5 pg/ml (P less than 0.001) in response to dbcAMP infusion. During phosphorus deprivation, serum phosphorus decreased from 4.1 +/- 0.8 to 3.2 +/- 1.2 mg/dl (P less than 0.05), but there was no change in serum 1,25(OH)2D concentration or any correlation between serum phosphorus and 1,25(OH)2D levels. Although reduction in mean serum phosphorus levels was generally not as great in patients with pseudohypoparathyroidism, one such patient attained serum phosphorus of 1.2 mg/dl and still did not increase serum 1,25(OH)2D concentration. In addition to an abnormal parathyroid hormone receptor-adenylate cyclase complex, patients with pseudohypoparathyroidism appear to have an abnormal renal 1 alpha-hydroxylase, which does not respond appropriately to phosphate deprivation.

Commercial kits for 1,25-dihydroxyvitamin D compared with a liquid-chromatographic assay

1993 ◽  
Vol 39 (6) ◽  
pp. 1086-1088 ◽  
Author(s):  
S Bertelloni ◽  
G I Baroncelli ◽  
U Benedetti ◽  
G Franchi ◽  
G Saggese
Keyword(s):  
Healthy Subjects ◽  
Clinical Work ◽  
Comparison Method ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Liquid Chromatographic Method ◽  
Commercial Kits ◽  
Liquid Chromatographic

Abstract Three commercially available kits for 1,25-dihydroxyvitamin D [1,25(OH)2D] determination were compared with a liquid-chromatographic method. Serum samples were analyzed for 1,25(OH)2D from 70 healthy subjects (age 2.2-17.5 years; 35 males, 35 females), some (n = 5) given orally high vitamin D3 doses. In addition, 1,25(OH)2D was measured in 28 patients with untreated diseases associated with low (n = 16) or high (n = 12) serum concentrations of the hormone. The results showed that the commercial kits were sufficiently accurate with respect to the comparison method and suitable for routine clinical work.

Effect of age on renal responsiveness to parathyroid hormone and calcitonin in rats

1987 ◽  
Vol 114 (2) ◽  
pp. 173-178 ◽  
Author(s):  
H. J. Armbrecht ◽  
N. Wongsurawat ◽  
R. E. Paschal
Keyword(s):  
Parathyroid Hormone ◽  
Age Groups ◽  
Phosphate Transport ◽  
Serum Concentrations ◽  
Adult Rats ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Old Adult

ABSTRACT The purpose of these studies was to determine whether the responsiveness of the kidney to parathyroid hormone (PTH) and calcitonin changed with age. Experiments were performed in young (3 months old), adult (12–14 months old) and old (22–24 months old) male Fischer 344 rats fed normal diets and thyroparathyroidectomized. Parathyroid hormone was administered i.p. at 24, 12 and 2 h before death and calcitonin was given i.p. at 12 and 2 h before death. Parathyroid hormone significantly increased the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) by renal slices from young but not adult or old animals. A similar age-related decline in the capacity of PTH to raise serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels was also seen. Parathyroid hormone significantly decreased tubular reabsorption of phosphorus, increased concentrations of urinary cyclic AMP (cAMP) and increased serum concentrations of calcium in all age groups. In contrast, calcitonin significantly increased 1,25-(OH)2D3 production by renal slices from both young and adult animals. Calcitonin decreased serum concentrations of calcium in young but not in adult rats. These results suggest that there are maturational changes in the PTH- and cAMP-dependent pathways in the kidney but not in the calcitonin- and cAMP-independent pathways. The changes in the PTH- and cAMP-dependent pathways affect the stimulation of 1,25-(OH)2D production but not the inhibition of phosphate transport. J. Endocr. (1987) 114, 173–178

scholarly journals Dietary Phosphorus Transcriptionally Regulates 25-Hydroxyvitamin D-1α-Hydroxylase Gene Expression in the Proximal Renal Tubule

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Martin Y. H. Zhang ◽  
Xuemei Wang ◽  
Jonathan T. Wang ◽  
Nathalie A. Compagnone ◽  
Synthia H. Mellon ◽  
...  
Keyword(s):  
Renal Tubule ◽  
Hydroxylase Activity ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Proximal Renal Tubule ◽  
1,25 Dihydroxyvitamin D ◽  
Dietary Phosphorus ◽  
Straight Tubules ◽  
25 Hydroxyvitamin D ◽  
Bowman's Capsule

Abstract Synthesis of the hormone 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, occurs in the kidney and is catalyzed by the mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase). We sought to characterize the effects of changes in dietary phosphorus on the kinetics of renal mitochondrial 1α-hydroxylase activity and the renal expression of P450c1α and P450c24 mRNA, to localize the nephron segments involved in such regulation, and to determine whether transcriptional mechanisms are involved. In intact mice, restriction of dietary phosphorus induced rapid, sustained, approximately 6- to 8-fold increases in renal mitochondrial 1α-hydroxylase activity and renal P450c1α mRNA abundance. Immunohistochemical analysis of renal sections from mice fed the control diet revealed the expression of 1α-hydroxylase protein in the proximal convoluted and straight tubules, epithelial cells of Bowman’s capsule, thick ascending limb of Henle’s loop, distal tubule, and collecting duct. In mice fed a phosphorusrestricted diet, immunoreactivity was significantly increased in the proximal convoluted and proximal straight tubules and epithelial cells of Bowman’s capsule, but not in the distal nephron. Dietary phosphorus restriction induced a 2-fold increase in P450c1α gene transcription, as shown by nuclear run-on assays. Thus, the increase in renal synthesis of 1,25-dihydroxyvitamin D induced in normal mice by restricting dietary phosphorus can be attributed to an increase in the renal abundance of P450c1α mRNA and protein. The increase in P450c1α gene expression, which occurs exclusively in the proximal renal tubule, is due at least in part to increased transcription of the P450c1α gene.

scholarly journals Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold.

1998 ◽  
Vol 9 (7) ◽  
pp. 1264-1269 ◽  
Author(s):  
D Prié ◽  
F B Blanchet ◽  
M Essig ◽  
J P Jourdain ◽  
G Friedlander
Keyword(s):  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Chronic Treatment ◽  
Serum Phosphorus ◽  
Calcium Excretion ◽  
Normal Range ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Renal Phosphate Reabsorption ◽  
A Prospective Study

It has been shown that an acute infusion of dipyridamole increased renal phosphate reabsorption in rats and humans. A prospective study was performed to determine whether chronic treatment by dipyridamole given orally could decrease renal phosphate leak and increase serum phosphorus in patients with idiopathic low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium, and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of patients within 3 mo, with maximal values reached within 9 mo. This improvement persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D concentrations were above the normal range (> 42 pg/ml) and normalized in parallel with the increase of serum phosphorus. The 24-h calcium excretion (which was initially increased in patients with high vitamin D concentrations) and urolithiasis decreased under treatment. Ionized serum calcium and parathyroid hormone remained unchanged. After 2 yr, treatment was discontinued in three patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses and can be used to treat these patients.

1,25-Dihydroxyvitamin D-stimulated calmodulin binding proteins: a sustained effect on distal tubules

2002 ◽  
Vol 282 (1) ◽  
pp. F77-F84 ◽  
Author(s):  
Emmanuel K. O. Siaw ◽  
Marian R. Walters
Keyword(s):  
Vitamin D ◽  
Time Course ◽  
Binding Proteins ◽  
Day Treatment ◽  
Rat Kidney ◽  
Vitamin D Receptors ◽  
Dihydroxyvitamin D ◽  
Calmodulin Binding ◽  
1,25 Dihydroxyvitamin D

The tubular localization of 1,25-dihydroxyvitamin D[1,25(OH)2D3]-stimulated calmodulin binding proteins (CaMBP-Ds) in the rat kidney and the specificity of their induction were characterized to better understand renal responses to protracted 1,25(OH)2D3 treatment in vivo. None of the other hormones tested (parathyroid hormone, calcitonin, estradiol-17β, testosterone, progesterone, hydrocortisone, or dexamethasone) stimulated the CaMBP-Ds, whereas maximal 1,25(OH)2D3 stimulation occurred after a 5- to 7-day treatment with 100 ng/day 1,25(OH)2D3. With the exception of the more ubiquitously distributed CaMBP-D150, the CaMBP-Ds were localized in distal, but not proximal, tubule preparations. 1,25(OH)2D3 induction of vitamin D receptors and the CaMBP-Ds was similar with respect to dose-response and time course. Finally, the CaMBP-Ds remained elevated for at least 4 wk after 1,25(OH)2D3 withdrawal. Because the vitamin D-stimulated renal CaMBP-Ds are principally proteins of the distal tubule, they may be associated with renal regulation of Ca2+ homeostasis. The sustained induction of CaMBP-Ds is important in addressing the question of whether their induction is a function of normal Ca2+ homeostasis or a pathophysiological consequence of hypervitaminosis D and hypercalcemia.

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