| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Oral Health and Diagnostic Sciences (S.M.M.), University of Connecticut School of Dental Medicine; Center for Molecular Medicine (S.M.M., J.J.G., Y.K.W., J.C.-G., K.S., A.A.) and Division of Endocrinology and Metabolism (A.A.), University of Connecticut School of Medicine, Farmington, Connecticut 06030-3101; and Brigham and Women’s Hospital (O.K., E.M.B.), Boston, Massachusetts 02115
Address all correspondence and requests for reprints to: Andrew Arnold, M.D., Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3101. E-mail: aarnold{at}nso2.uchc.edu.
The properties of neoplastic proliferation and hormonal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether abnormal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal sequence of these fundamental abnormalities in a mouse model of primary HPT. These transgenic mice (PTH-D1) harbor a transgene that targets overexpression of the cyclin D1 oncogene to parathyroid cells, resulting in parathyroid hypercellularity with a phenotype of chronic biochemical HPT and, notably, an abnormal in vivo PTH-calcium set point. We examined parathyroid cell proliferation and biochemical alterations in PTH-D1 and control wild-type mice from ages 1–14 months. Strikingly, abnormal parathyroid proliferation regularly preceded dysregulation of the calcium-PTH axis, supporting the concept that disturbed parathyroid proliferation is the crucial primary initiator leading to the development of the biochemical phenotype of HPT. Furthermore, we observed that decreased expression of the calcium-sensing receptor in the parathyroid glands occurs several months before development of biochemical HPT, suggesting that decreased calcium-sensing receptor may not be sufficient to cause PTH dysregulation in this animal model of primary HPT.
This article has been cited by other articles:
 |
|
 |
|
  T. Kawata, Y. Imanishi, K. Kobayashi, T. Miki, A. Arnold, M. Inaba, and Y. Nishizawa Parathyroid Hormone Regulates Fibroblast Growth Factor-23 in a Mouse Model of Primary Hyperparathyroidism J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2683 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wettschureck, E. Lee, S. K. Libutti, S. Offermanns, P. G. Robey, and A. M. Spiegel Parathyroid-Specific Double Knockout of Gq and G11 {alpha}-Subunits Leads to a Phenotype Resembling Germline Knockout of the Extracellular Ca2+-Sensing Receptor Mol. Endocrinol., January 1, 2007; 21(1): 274 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Scillitani, V. Guarnieri, C. Battista, S. De Geronimo, L. A. Muscarella, I. Chiodini, M. Cignarelli, S. Minisola, F. Bertoldo, C. M. Francucci, et al. Primary Hyperparathyroidism and the Presence of Kidney Stones Are Associated with Different Haplotypes of the Calcium-Sensing Receptor J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Samander and A. Arnold Mutational Analysis of the Vitamin D Receptor Does Not Support Its Candidacy as a Tumor Suppressor Gene in Parathyroid Adenomas J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5019 - 5021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Suva PTH Expression, Not Always where You Think ... J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 396 - 397. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
