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

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.

2012 ◽  
Vol 92 (1) ◽  
pp. 131-155 ◽  
Author(s):  
Aline Martin ◽  
Valentin David ◽  
L. Darryl Quarles

Calcium (Ca2+) and phosphate (PO43−) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca2+ levels by increasing Ca2+ reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)2D] production by the kidney, enhancing Ca2+ and PO43− intestinal absorption and increasing Ca2+ and PO43− efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)2D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)2D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO43− handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts.


1985 ◽  
Vol 69 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Peter L. Selby ◽  
Munro Peacock ◽  
Stuart A. Barkworth ◽  
Wendy B. Brown ◽  
Geoffrey A. Taylor

1. The early effects of sex steroid therapy were assessed in 28 normal post-menopausal women, 18 treated with ethinyloestradiol and 10 with norethisterone. 2. There was a reduction in the fasting urinary excretion of both calcium and hydroxyproline with both treatments, indicating reduced bone resorption. This was apparent after 1 week of therapy but became more marked after 3 weeks. 3. These changes were not accompanied by any changes in plasma levels of calcitonin or parathyroid hormone. 4. Patients receiving ethinyloestradiol showed a marked increase in plasma 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentration but this was explicable entirely in terms of increased plasma levels of vitamin D binding protein. There was no change in the free plasma level of 1,25(OH)2D. Patients treated with norethisterone showed no increase in plasma concentrations of 1,25(OH)2D. 5. We conclude that both ethinyloestradiol and norethisterone have a rapid and similar effect in reducing bone resorption. This is not mediated via the plasma levels of the calcium regulating hormones.


1998 ◽  
Vol 9 (7) ◽  
pp. 1264-1269 ◽  
Author(s):  
D Prié ◽  
F B Blanchet ◽  
M Essig ◽  
J P Jourdain ◽  
G Friedlander

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.


1996 ◽  
Vol 270 (3) ◽  
pp. E483-E490
Author(s):  
A. A. Portale ◽  
B. P. Halloran ◽  
R. C. Morris ◽  
E. T. Lonergan

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.


2002 ◽  
Vol 282 (1) ◽  
pp. F77-F84 ◽  
Author(s):  
Emmanuel K. O. Siaw ◽  
Marian R. Walters

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.


2002 ◽  
pp. 635-642 ◽  
Author(s):  
L Rejnmark ◽  
AL Lauridsen ◽  
P Vestergaard ◽  
L Heickendorff ◽  
F Andreasen ◽  
...  

OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.


2004 ◽  
Vol 89-90 ◽  
pp. 533-537 ◽  
Author(s):  
Elizabeth T. Jacobs ◽  
Anna R. Giuliano ◽  
Marı́a Elena Martı́nez ◽  
Bruce W. Hollis ◽  
Mary E. Reid ◽  
...  

2007 ◽  
Vol 292 (6) ◽  
pp. E1917-E1921 ◽  
Author(s):  
Katie Beth Williams ◽  
Hector F. DeLuca

A new, completely in vivo method of measuring the rate of intestinal phosphate absorption has been developed. As expected from previous in vitro and ex vivo measurements, intestinal phosphate absorption is potently and rapidly stimulated by 1,25-dihydroxyvitamin D3. The response is saturated with as little as 11.3 ng of 1,25-dihydroxyvitamin D3 per day, consistent with a genomic mechanism. The effect of 1,25-dihydroxyvitamin D3 disappears when the dosing solution of phosphate is at 2 M, suggesting that 1,25-dihydroxyvitamin D3 stimulates active transport of phosphate but not diffusion of phosphate. Finally, unlike findings resulting from in vitro or ex vivo experiments, no evidence in vivo was obtained that phosphate absorption requires sodium or is inhibited by potassium.


Sign in / Sign up

Export Citation Format

Share Document