| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 22, 2003
Accepted on December 12, 2003
1 Calcium Research Laboratory and Department of Medicine, McGill University Health Centre and Royal Victoria Hospital, McGill University, Montreal, Canada H3A 1A1; Department of Medicine and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2; Department of Oral and Developmental Biology, Forsyth Institute and Harvard School of Dental Medicine, Boston, MA 02115
* To whom correspondence should be addressed. E-mail: akarapli{at}ldi.jgh.mcgill.ca.
We have examined the role of parathyroid hormone (PTH) in the postnatal state in a mouse model of PTH deficiency generated by targeting the Pth gene in ES cells. Mice homozygous for the ablated allele, when maintained on a normal calcium intake, developed hypocalcemia, hyperphosphatemia, and low circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels consistent with primary hypoparathyroidism. Bone turnover was reduced, leading to increased trabecular and cortical bone volume in PTH-deficient mice. When mutant mice were placed on a low calcium diet, renal 25-hydroxyvitamin D 1 
-hydroxylase (Cyp27b1) expression increased despite the absence of PTH, leading to a rise in circulating 1,25(OH)2D3 levels, marked osteoclastogenesis, and profound bone resorption. These studies demonstrate the dependence of the skeletal phenotype in animals with genetically depleted PTH on the external environment as well as on internal hormonal and ionic circulatory factors. They show that while PTH action is the first defense against hypocalcemia, 1,25(OH)2D3 can be mobilized, even in the absence of PTH, to guard against extreme calcium deficiency.
This article has been cited by other articles:
 |
|
 |
|
  C. Galli, L. A. Zella, J. A. Fretz, Q. Fu, J. W. Pike, R. S. Weinstein, S. C. Manolagas, and C. A. O'Brien Targeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-{kappa}B Ligand Gene Reduces Bone Remodeling and Increases Bone Mass Endocrinology, January 1, 2008; 149(1): 146 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Bai, D. Miao, D. Goltzman, and A. C. Karaplis Early Lethality in Hyp Mice with Targeted Deletion of Pth Gene Endocrinology, October 1, 2007; 148(10): 4974 - 4983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xue, A. C. Karaplis, G. N. Hendy, D. Goltzman, and D. Miao Exogenous 1,25-Dihydroxyvitamin D3 Exerts a Skeletal Anabolic Effect and Improves Mineral Ion Homeostasis in Mice that Are Homozygous for Both the 1{alpha}-Hydroxylase and Parathyroid Hormone Null Alleles Endocrinology, October 1, 2006; 147(10): 4801 - 4810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Fu, S. C. Manolagas, and C. A. O'Brien Parathyroid Hormone Controls Receptor Activator of NF-{kappa}B Ligand Gene Expression via a Distant Transcriptional Enhancer. Mol. Cell. Biol., September 1, 2006; 26(17): 6453 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Teegarden, P. Legowski, C. W. Gunther, G. P. McCabe, M. Peacock, and R. M. Lyle Dietary Calcium Intake Protects Women Consuming Oral Contraceptives from Spine and Hip Bone Loss J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5127 - 5133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xue, A. C. Karaplis, G. N. Hendy, D. Goltzman, and D. Miao Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D3 play distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal development Hum. Mol. Genet., June 1, 2005; 14(11): 1515 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xu, S. Choudhary, D. Goltzman, F. Ledgard, D. Adams, G. Gronowicz, B. Koczon-Jaremko, L. Raisz, and C. Pilbeam Do Cyclooxygenase-2 Knockout Mice Have Primary Hyperparathyroidism? Endocrinology, April 1, 2005; 146(4): 1843 - 1853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Warden, A. G. Robling, M. S. Sanders, M. M. Bliziotes, and C. H. Turner Inhibition of the Serotonin (5-Hydroxytryptamine) Transporter Reduces Bone Accrual during Growth Endocrinology, February 1, 2005; 146(2): 685 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Bai, D. Miao, J. Li, D. Goltzman, and A. C. Karaplis Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders Endocrinology, November 1, 2004; 145(11): 5269 - 5279. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
