Normal vitamin D receptor concentration and responsiveness to 1,95-Dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria

J. E. Zerwekh, B. Y. Reed, H. J. Heller, G. B. Gonzalez, M. R. Haussler, C. Y C Pak

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric ciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 ± 11 vs. 30 ± 15 ng/mg protein, respectively) or following 1,25(OH)2D3-mediated upregulation (43 ± 18 vs. 42 ± 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/P-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 ± 1.7 vs. 1.8 ± 2.4) or following (2.7 ± 2.8 vs. 1.9 ± 1.8) 1,25(OH)2D3 exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)2D3-mediated induction of 25-hydroxyvitamin D3-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 ± 1.6 vs. 1.9 ± 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1,25(OH)2D3 in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.

Original languageEnglish (US)
Pages (from-to)307-313
Number of pages7
JournalMineral and Electrolyte Metabolism
Volume24
Issue number5
StatePublished - 1998

Fingerprint

Hypercalciuria
Calcitriol Receptors
Fibroblasts
Skin
Messenger RNA
Up-Regulation
Calcium
Calcifediol
dihydroxy-vitamin D3
Calcitriol
Intestinal Absorption
Mixed Function Oxygenases
Bioactivity
Vitamin D
Actins
Proteins

Keywords

  • 24-Hydroxylase
  • Absorptive hypercalciuria
  • Skin fibroblasts
  • Vitamin D receptor
  • Vitamin D receptor mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Normal vitamin D receptor concentration and responsiveness to 1,95-Dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria. / Zerwekh, J. E.; Reed, B. Y.; Heller, H. J.; Gonzalez, G. B.; Haussler, M. R.; Pak, C. Y C.

In: Mineral and Electrolyte Metabolism, Vol. 24, No. 5, 1998, p. 307-313.

Research output: Contribution to journalArticle

@article{39ca8aeb8dc04ffa89fd0f8c71db2a8e,
title = "Normal vitamin D receptor concentration and responsiveness to 1,95-Dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria",
abstract = "To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric ciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 ± 11 vs. 30 ± 15 ng/mg protein, respectively) or following 1,25(OH)2D3-mediated upregulation (43 ± 18 vs. 42 ± 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/P-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 ± 1.7 vs. 1.8 ± 2.4) or following (2.7 ± 2.8 vs. 1.9 ± 1.8) 1,25(OH)2D3 exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)2D3-mediated induction of 25-hydroxyvitamin D3-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 ± 1.6 vs. 1.9 ± 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1,25(OH)2D3 in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.",
keywords = "24-Hydroxylase, Absorptive hypercalciuria, Skin fibroblasts, Vitamin D receptor, Vitamin D receptor mRNA",
author = "Zerwekh, {J. E.} and Reed, {B. Y.} and Heller, {H. J.} and Gonzalez, {G. B.} and Haussler, {M. R.} and Pak, {C. Y C}",
year = "1998",
language = "English (US)",
volume = "24",
pages = "307--313",
journal = "Mineral and Electrolyte Metabolism",
issn = "0378-0392",
publisher = "S. Karger AG",
number = "5",

}

TY - JOUR

T1 - Normal vitamin D receptor concentration and responsiveness to 1,95-Dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria

AU - Zerwekh, J. E.

AU - Reed, B. Y.

AU - Heller, H. J.

AU - Gonzalez, G. B.

AU - Haussler, M. R.

AU - Pak, C. Y C

PY - 1998

Y1 - 1998

N2 - To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric ciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 ± 11 vs. 30 ± 15 ng/mg protein, respectively) or following 1,25(OH)2D3-mediated upregulation (43 ± 18 vs. 42 ± 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/P-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 ± 1.7 vs. 1.8 ± 2.4) or following (2.7 ± 2.8 vs. 1.9 ± 1.8) 1,25(OH)2D3 exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)2D3-mediated induction of 25-hydroxyvitamin D3-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 ± 1.6 vs. 1.9 ± 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1,25(OH)2D3 in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.

AB - To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric ciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 ± 11 vs. 30 ± 15 ng/mg protein, respectively) or following 1,25(OH)2D3-mediated upregulation (43 ± 18 vs. 42 ± 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/P-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 ± 1.7 vs. 1.8 ± 2.4) or following (2.7 ± 2.8 vs. 1.9 ± 1.8) 1,25(OH)2D3 exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)2D3-mediated induction of 25-hydroxyvitamin D3-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 ± 1.6 vs. 1.9 ± 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1,25(OH)2D3 in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.

KW - 24-Hydroxylase

KW - Absorptive hypercalciuria

KW - Skin fibroblasts

KW - Vitamin D receptor

KW - Vitamin D receptor mRNA

UR - http://www.scopus.com/inward/record.url?scp=0031827076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031827076&partnerID=8YFLogxK

M3 - Article

C2 - 9705566

AN - SCOPUS:0031827076

VL - 24

SP - 307

EP - 313

JO - Mineral and Electrolyte Metabolism

JF - Mineral and Electrolyte Metabolism

SN - 0378-0392

IS - 5

ER -