scholarly journals Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults

2015 ◽  
Vol 100 (10) ◽  
pp. 3668-3675 ◽  
Author(s):  
Aneta Gawlik ◽  
Vardit Gepstein ◽  
Nimrod Rozen ◽  
Aviva Dahan ◽  
Dafna Ben-Yosef ◽  
...  

Context: Puberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty. Objectives: To investigate duodenal 25-hydroxy vitamin D-1α-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and adults. Design and Methods: CYP27B1and IGF1 mRNA expression and 1,25(OH)2D3 production were determined in duodenal biopsies. CYP27B1 expression was also determined after IGF1R inhibitor treatment of human and mice duodenal explants. mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by incubating duodenal explants with 25(OH)D3 and measuring 1,25(OH)2D3 production by radioimmunoassay. Results: CYP27B1 mRNA expression was 13.7 and 10.4 times higher in biopsies from adolescents compared to adults and children, respectively. IGF1 mRNA expression was 30% and 45% higher in explants from adolescents and children, respectively, compared to adults. Inhibition of IGF1 receptor activity decreased CYP27B1expression in explants from both mice (85%) and humans (24%). 1,25(OH)2D3 production reached a maximum velocity of 768 ± 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 in children and adolescents, whereas the maximum velocity was 86.4 ± 43.2 pmol/l/mg protein in adults. The substrate concentration at which the enzyme shows half of its maximum activity was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D3. Conclusions: Increased CYP27B1 expression and local duodenal 1,25(OH)2D3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.

1986 ◽  
Vol 251 (1) ◽  
pp. G14-G18
Author(s):  
P. Ammann ◽  
R. Rizzoli ◽  
H. Fleisch

Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of 45CaCl2 into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the 45CaCl2 injected disappeared. This absorption was modulated by 1,25-dihydroxyvitamin D3, increased to 64.0 +/- 4.2% under a low-Ca diet, and increased under low-Pi diet. In contrast, when the difference of nonradioactive Ca in the cecal content and the feces was measured, only 4.1 +/- 4.6% (not significant) was absorbed. Secretion of intravenously injected 45Ca into the lumen was small and not altered by any of the conditions tested. When cecum contents were placed into duodenal tied loops, 14 +/- 6.2% were absorbed in situ when 45Ca was given orally, whereas when 45Ca was directly added to the content 35.6 +/- 4.6% were absorbed (P less than 0.02). These results indicate that the large intestine has an important vitamin D-dependent Ca absorptive system detectable if 45Ca is injected into the cecum. However, it is not effective in vivo because the Ca arriving in the large intestine appears to be no longer in an absorbable form.


Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3885-3894 ◽  
Author(s):  
Yurong Song ◽  
Xiaorong Peng ◽  
Angela Porta ◽  
Hitomi Takanaga ◽  
Ji-Bin Peng ◽  
...  

Abstract We examined the expression of calcium transporter 1 (CaT1) and epithelial calcium channel (ECaC) mRNA in the duodenum and kidney of mice. Intestinal CaT1 mRNA level increased 30-fold at weaning, coincident with the induction of calbindin-D9k expression. In contrast, renal CaT1 and ECaC mRNA expression was equal until weaning when ECaC mRNA is induced and CaT1 mRNA levels fall 70%. Long- and short-term adaptation to changes in dietary calcium (Ca) level and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] injection strongly regulated duodenal calbindin D9k and CaT1 mRNA. Following a single dose of 1,25(OH)2D3, induction of CaT1 mRNA occurred rapidly (within 3 h, peak at 6 h of 9.6 ± 0.8-fold) and preceded the induction of intestinal Ca absorption (significantly increased at 6 h, peak at 9 h). Neither renal CaT1 nor ECaC mRNA were strongly regulated by dietary calcium level or 1,25(OH)2D3 injection. Our data indicate that CaT1 and ECaC mRNA levels are differentially regulated by 1,25(OH)2D3 in kidney and intestine and that there may be a specialized role for CaT1 in kidney in fetal and neonatal development. The rapid induction of intestinal CaT1 mRNA expression by 1,25(OH)2D3, and the marked induction at weaning, suggest that CaT1 is critical for 1,25(OH)2D3-mediated intestinal Ca absorption.


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.


2002 ◽  
Vol 72 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Susan J. Fairweather-Tait ◽  
Birgit Teucher

A well established stable isotope technique exists for measuring calcium absorption from single foods and meals, but the long term effects of calcium on bone health cannot be assessed from acute bioavailability studies. Bone health depends primarily on the degree of mineralization, measured as bone mineral density (BMD), and phenotypic variations depend on genetic and environmental factors including calcium supply. Since almost all retained calcium is used for bone mineralization and remodeling, BMD can be used as a long-term (> six months) marker of dietary calcium bioavailability. However, BMD is a very insensitive marker of calcium bioavailability, so its use in dietary intervention studies is restricted to periods of significant bone growth or loss. Biochemical markers of bone metabolism may be used to predict the overall bioavailability of dietary calcium over a shorter time period (> four weeks), but they have a high coefficient of variation, so may not be appropriate for some dietary intervention studies. A group of European laboratories is currently developing an alternative approach using a long-lived radioisotope (41Ca) to label bone calcium and to directly measure the rate of calcium loss from urinary excretion data. The efficiency of calcium absorption is inversely related to intake; whole body balance of the mineral is dependent on rates of absorption and excretion and limited by calcium-binding substances in the gut. Dietary data and indirect measures of bone health indicate that bioavailability is important when habitual intakes are low, especially during periods of bone growth or loss. Further research is required to quantify the effects of major dietary modulators of calcium balance on bone health and to understand their relationship with genetic and physiological variables.


1975 ◽  
Vol 229 (2) ◽  
pp. 402-408 ◽  
Author(s):  
JP Bonjour ◽  
U Trechsel ◽  
H Fleisch ◽  
R Schenk ◽  
HF DeLuca ◽  
...  

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.


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