Skip Navigation



NDT Advance Access published online on October 12, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi186
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/3/644    most recent
gfi186v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Brown, A. J.
Right arrow Articles by Strugnell, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, A. J.
Right arrow Articles by Strugnell, S. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 17, 2005
Accepted September 7, 2005

Original Articles

The vitamin D prodrugs 1{alpha}(OH)D2, 1{alpha}(OH)D3 and BCI-210 suppress PTH secretion by bovine parathyroid cells

Alex J. Brown 1*, Cynthia S. Ritter 1, Joyce C. Knutson 2, and Stephen A. Strugnell 2

1 Renal Division, Washington University School of Medicine, St Louis, MO
2 Preclinical Research, Bone Care International, Middleton, WI, USA

* To whom correspondence should be addressed.
Alex J. Brown, E-mail: abrown{at}imgate.wustl.edu



  Abstract

Background. Active vitamin D compounds are widely used in the treatment of secondary hyperparathyroidism associated with renal failure. These compounds reduce PTH secretion through vitamin D receptor (VDR)-dependent repression of PTH gene transcription. In previous studies, 1{alpha}(OH)D3, a vitamin D prodrug, inhibited PTH secretion in cultured bovine parathyroid cells, but it was unclear whether 1{alpha}(OH)D3 itself or an active metabolite produced this inhibition.

Methods. We determined the effectiveness of the vitamin D prodrugs 1{alpha}(OH)D3, 1{alpha}(OH)D2 and 1{alpha}(OH)-24(R)-methyl-25-ene-D2 (BCI-210) at inhibiting PTH secretion in bovine parathyroid cell cultures, and examined the metabolism of [3H]1{alpha}(OH)D2 in these cells.

Results. All three prodrugs suppressed PTH secretion with approximately 10% of the activity of 1,25(OH)2D3; much higher activity than expected based on the VDR affinities of these prodrugs (0.25% of 1,25(OH)2D3). Parathyroid cells activated [3H]1{alpha}(OH)D2 to both 1,25(OH)2D2 and 1,24(OH)2D2. 1,24(OH)2D2 was detectable at 4 h, increased to a maximum at 8 h, and then decreased. In contrast, 1,25(OH)2D2 levels increased linearly with time, suggesting the presence of constitutively active vitamin D-25-hydroxylase not previously reported in parathyroid cells. The cytochrome P-450 inhibitor ketoconazole (50 µM) reduced 1{alpha}(OH)D2 metabolism to below detectable levels, but did not significantly affect suppression of PTH by 1{alpha}(OH)D2.

Conclusions. The vitamin D prodrugs 1{alpha}(OH)D3, 1{alpha}(OH)D2 and BCI-210 suppressed PTH production by cultured parathyroid cells. The ability of 1{alpha}(OH)D2 to reduce PTH despite inhibition of its metabolism suggests a direct action of this ‘prodrug’ on the parathyroid gland, but the mechanism underlying this activity is not yet known.

Keywords: BCI-210; 1{alpha}-hydroxyvitamin D2; 1{alpha}-hydroxyvitamin D3; ketoconazole; parathyroid hormone; vitamin D.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J EndocrinolHome page
I. Mohamed and J. K Yeh
Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats
J. Endocrinol., August 1, 2009; 202(2): 317 - 325.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.