Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats.

Yao, J. C.; Kathpalia, Paru P.; Bushinsky, David A.; Favus, Murray J.

doi:10.1172/jci1164

Cited by 94 publications

(98 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, PTH induced a similar degree of bone resorption in control and GHS rat calvariae. Immunoblot analysis demonstrated a fourfold increase in the level of vitamin D receptors in GHS rat calvariae compared with control calvariae, similar to the increased intestinal receptors described previously (22,30). There was no comparable change in vitamin D receptor RNA levels as measured by slot blot analysis, suggesting the altered regulation of the vitamin D receptor occurs posttranscriptionally.…”

Section: Genetic Hypercalciuric Stone-forming Ratssupporting

confidence: 77%

“…The finding of increased intestinal calcium absorption without an elevation in 1,25(OH) 2 D 3 levels led Li et al to hypothesize that alteration of the receptor for vitamin D might be responsible for the abnormal regulation of calcium by enterocytes (22,143). The intensity of 1,25(OH) 2 D 3 action correlates with receptor number and saturation (144,145) both in rats in vivo (146 -148) and in cell culture studies in vitro (149,150 Yao et al (30) found that the vitamin D receptor in the GHS rats hyperresponded to minimal doses of 1,25(OH) 2 D 3 . The hyperresponsiveness occurred through an increase in vitamin D receptor stability without involving alterations in VDR gene transcription, de novo protein synthesis, or mRNA sequence.…”

Section: Genetic Hypercalciuric Stone-forming Ratsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

View full text Add to dashboard Cite

Section: Genetic Hypercalciuric Stone-forming Ratssupporting

confidence: 77%

Section: Genetic Hypercalciuric Stone-forming Ratsmentioning

confidence: 99%

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

View full text Add to dashboard Cite

“…However, significantly higher levels of vitamin D receptors (VDR) have been found in bone, kidney and intestine, compared to normal rats, which would explain the increased sensitivity to 1,25(OH) 2 D 3 that was found in tissues taken from GHS rats [21]. In the gut, vitamin D-responsive genes are expressed at increased levels in response to small doses of 1,25(OH) 2 D 3 [22], with consequent increased expression of proteins related to calcium homeostasis, such as epithelial calcium channels (TRPV6 in gut), and calbindins. The calcium sensing receptor (CaSR) is another 1,25(OH) 2 D 3 -responsive gene, and increased levels of CaSR protein and mRNA have also been found in the kidneys of GHS rats compared to control rats fed the same diet [23].…”

Section: The Genetic Hypercalciuric Ratmentioning

confidence: 99%

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Worcester

Coe

2008

Seminars in Nephrology

146

125

View full text Add to dashboard Cite

Idiopathic hypercalciuria (IH) is the commonest metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is above 250 mg/day in women and 300 mg/day in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, negative calcium balance is commonly seen in balance studies, especially on a low calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered PTH levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients. Definition of HypercalciuriaCalcium, the most abundant cation in human beings, is an important participant in many physiologic processes, including hormonal secretion, cardiac contraction, blood clotting, and neurotransmission. In addition, growth and repair of our skeleton demands an adequate supply of calcium, and careful maintenance of extracellular calcium concentrations. For this reason, prevailing levels of intracellular and extracellular calcium are tightly regulated, by a complex system of control mechanisms. These mechanisms control calcium absorption by gut and renal tubular epithelia, as well as fluxes of calcium on and off bone, during varying dietary calcium intakes. In healthy, non-pregnant adults, whose skeleton is no longer growing, net intestinal calcium absorption is matched by renal excretion, and provides sufficient calcium for skeletal maintenance; however, under pathologic conditions, some urine calcium may derive from bone loss.Abnormalities of calcium homeostasis could result in a number of undesired consequences, including abnormally high or low serum calcium levels, or inadequate maintenance of bone mineral. Hypercalciuria might be defined as any level of urine calcium that exceeds net intestinal absorption, leading to net loss of calcium. However, in practice net intestinal absorption is seldom measured, and under the assumption that urine calcium is primarily derived from intestinal absorption, the working definition of hypercalciuria is urine calcium excretion that exceeds that found in the majority of healthy adults eating their usual diets. In practice, this is usually defined as a daily calcium excretion over 250 mg/day in women or 300Mailing address: Elaine Worcester, M.D., Nephrology Section, Suite 511 / MC 5100, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, Phone: 773-702-7459, Fax: 773-702-5818. Publisher's Disclaimer: This is a PDF file ...

show abstract

“…Every 2 wk 24-hr urine collections were obtained. Individual urine collections for the 24 rats divided into the two groups were analyzed separately and were then averaged for the first 6 wk (weeks 1-6), the second 6 wk (weeks [7][8][9][10][11][12], and the final 6 wk (weeks 13-18). Ctl, GHS rats fed a standard 1.2% calcium diet with 5% hydroxyproline added; Thz, rats fed as in Ctl with added chlorthalidone (Thz, 1 mg/15 g of food to provide approximately 4 to 5 mg/kg body weight per 24 h); *, different from Ctl same time period, P Ͻ 0.05. the second and third time periods, Thz induced a significant decrease in urine pH; however, during the first time period, there was no difference in urine pH between the two groups ( Figure 2, top).…”

Section: Urine Ion Excretion Volume and Phmentioning

confidence: 99%

Thiazides Reduce Brushite, but not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone–Forming Rats

Bushinsky¹,

Asplin²

2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-L-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.

show abstract

Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats.

Cited by 94 publications

References 37 publications

Molecular Mechanisms of Primary Hypercalciuria

Molecular Mechanisms of Primary Hypercalciuria

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

Thiazides Reduce Brushite, but not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone–Forming Rats

Contact Info

Product

Resources

About