Mechanism of the regulation of the 1α,25-dihydroxyvitamin D3 receptor in the rat jejunum by glucocorticoids

1984 ◽  
Vol 103 (3) ◽  
pp. 295-300 ◽  
Author(s):  
S. D. H. Chan ◽  
D. K. H. Chiu ◽  
D. Atkins

ABSTRACT The distribution of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptors in isolated jejunal villous and crypt cells was investigated in normal and adrenalectomized male rats, and also in animals treated with the synthetic glucocorticoid, dexamethasone, and/or the glucocorticoid antagonist, 11-deoxycortisol. Adrenalectomy caused an increase in 1,25-(OH)2D3 receptors whilst dexamethasone treatment led to a reduction in receptor number. 11-Deoxycortisol was able to reverse the 'down-regulation' effect caused by glucocorticoids. In all cases, the changes in receptor numbers were more pronounced in crypt cells. The data suggest that, in the small intestine, glucocorticoids may control the synthesis of 1,25-(OH)2D3 receptors via the mediation of a glucocorticoid receptor, and that the adrenal hormones mainly express their effect in crypt cells. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs in man after chronic glucocorticoid treatment. J. Endocr. (1984) 103, 295–300

1997 ◽  
Vol 272 (3) ◽  
pp. E422-E428 ◽  
Author(s):  
A. J. Sips ◽  
R. Barto ◽  
J. C. Netelenbos ◽  
W. J. van der Vijgh

The applicability of stable strontium as a marker for measuring intestinal calcium absorption is mainly dependent on the validity of the assumption that calcium and strontium are absorbed with a constant ratio. Up to now, it is not clear whether this ratio is affected by intervention therapy. Therefore, preclinical screening of this ratio before and after treatment is indispensable for a clinical calcium absorption test based on the use of stable strontium as a marker. We studied the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D(3)], a potent enhancer of active intestinal calcium absorption, on the pharmacokinetics of both calcium-45 and strontium in adult male rats, in a short-term dose-finding study [0-50 ng 1,25(OH)2D(3)/100 g body weight] and also in a placebo-controlled study in which 12.5 ng 1,25(OH)2D(3)/100 g body weight were applied to assess the long-term pharmacokinetics. The mean bioavailability (true absorption) was 33% for calcium and 19% for strontium (ratio 1.7:1), whereas, after 1,25(OH)2D(3) pretreatment, it was 73 and 43% (ratio 1.7:1), respectively. These findings demonstrate that intestinal strontium absorption has, like intestinal calcium absorption, an active component. Moreover, they underscore the applicability of stable strontium as a tool for investigating calcium absorption under various conditions.


1986 ◽  
Vol 113 (1) ◽  
pp. 96-103 ◽  
Author(s):  
Heide S. Cross ◽  
Doris Pölzleitner ◽  
Meinrad Peterlik

Abstract. Thyroxine (T4) and triiodothyronine (T3) activate Na+-dependent inorganic phosphate (Pi) transport in organ-cultured embryonic chick small intestine. Induction of transport activity requires intact protein synthesis and can be expressed in enterocytes with varying degrees of differentiation. T3 and T4 exert their effect independent of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is shown to stimulate Pi uptake only in the final stage of embryonic differentiation. At this time point, a potentiating effect of 1,25(OH)2D3 and T4 on Pi transport in cultured jejunum can be demonstrated. Thyroid hormones appear to stimulate Na+ gradient-driven Pi transport without concomitantly raising (Na+-K+)-ATPase activity. T4 has no influence whatsoever on calcium uptake by cultured embryonic small intestine while 1,25(OH)2D3 is effective at all stages of embryonic development investigated (day 15–20). However, when both hormones were present in the culture medium, the effect of 1,25(OH)2D3 on calcium transport is doubled. Our results suggest that the hyperphosphataemia associated with hyperthyroidism is likely to result, at least in part, from the independent effect of thyroid hormones as well as from their potentiation of the 1,25(OH)2D3 action on Na+-dependent intestinal Pi transport. In addition, their permissive effect on 1,25(OH)2D3-induced calcium absorption provides an explanation for unaltered calcium absorption in a number of hyperthyroid patients, although reduced plasma levels of 1,25(OH)2D3 are generally observed in this condition.


2004 ◽  
Vol 286 (4) ◽  
pp. F739-F748 ◽  
Author(s):  
Angela J. Brewer ◽  
Lucie Canaff ◽  
Geoffrey N. Hendy ◽  
Harriet S. Tenenhouse

Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, a renal phosphate-wasting disorder associated with defective skeletal mineralization. PHEX is predominantly expressed in bones and teeth and in the parathyroid gland of patients with chronic renal failure and tertiary hyperparathyroidism. The purpose of the present study was to examine the effects of renal insufficiency and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the regulation of PHEX expression in rat tibia and parathyroid gland. In rats fed a high-phosphate (Pi) diet, ⅚ nephrectomy elicited a significant increase in the serum parathyroid hormone (PTH) concentration that was associated with a significant increase in the abundance of PHEX mRNA and protein in the tibia and a significant increase in PHEX mRNA in the parathyroid gland. In contrast, 1,25(OH)2D3 administration to intact rats fed a control diet elicited a significant decrease in the serum PTH concentration that was accompanied by a significant decrease in PHEX mRNA and protein abundance in the tibia and a significant decrease in PHEX mRNA in the parathyroid gland. In addition, the increases in serum PTH levels and PHEX mRNA in the tibia and parathyroid gland in ⅚ nephrectomized rats fed a high-Pi diet were blunted by 1,25(OH)2D3. Serum PTH concentration was positively and significantly correlated with tibial PHEX mRNA and protein abundance. In summary, we demonstrate that PHEX expression in the tibia and parathyroid gland is increased by chronic renal insufficiency and decreased by 1,25(OH)2D3 administration and suggest that PTH status may play an important role in mediating these changes in PHEX expression.


1984 ◽  
Vol 67 (3) ◽  
pp. 285-290 ◽  
Author(s):  
S. D. H. Chan ◽  
D. Atkins

1. The distribution of the 1α,25-dihydroxycholecalciferol receptor was studied in enterocytes isolated from the upper, mid and lower villus and crypt cells of the jejunum of normal and rachitic rats. 2. In all cell fractions a high-affinity receptor (KD ⋍ 0.07 nmol/l) with a sedimentation coefficient of 3.5S was demonstrated. 3. In normal rats there was a 60% reduction in receptor numbers in crypt cells compared with the mid and upper villous cells. 4. Vitamin D deficiency led to a reduction in receptor numbers in all cell fractions (45% upper villus, 78% crypt cells). 5. The data are compatible with the concept of calcium absorption occurring in the differentiated villous cells and also account for the reduction in absorption in rachitic animals.


1999 ◽  
Vol 73 (7) ◽  
pp. 367-372 ◽  
Author(s):  
Tadashi Furukawa ◽  
Sunao Manabe ◽  
Toshiyuki Watanabe ◽  
Shinya Sehata ◽  
Satoru Sharyo ◽  
...  

Author(s):  
Igor N. Sergeev

AbstractModulation of apoptosis is emerging as a promising strategy for prevention and treatment of breast cancer and obesity because removal of mammary cancer cells and mature adipocytes through this process will result in decreasing tumor size and produce long-term reduction in adipose tissue mass. The hormone 1,25-dihydroxyvitamin D


1991 ◽  
Vol 260 (2) ◽  
pp. E220-E225 ◽  
Author(s):  
J. Fox

Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores.


2003 ◽  
Vol 10 (6) ◽  
pp. 1129-1135 ◽  
Author(s):  
S. G. Rhodes ◽  
L. A. Terry ◽  
J. Hope ◽  
R. G. Hewinson ◽  
H. M. Vordermeier

ABSTRACT This report describes the presence and activity of 1,25-dihydroxyvitamin D3 (1,25-D3) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D3 within the first 2 weeks following infection with Mycobacterium bovis. 1,25-D3-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D3 both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.


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