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Received on July 26, 2004
Accepted on September 24, 2004
Endocrinology and Metabolism |
1 Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Saint-Luc and
Medicine, Hôpital Saint-Luc and Université de Montréal, Montréal, Québec, Canada
2 Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Saint-Luc and
Biochemistry, Hôpital Saint-Luc and Université de Montréal, Montréal, Québec, Canada
3 Scantibodies Laboratory Inc., Santee, CA
* To whom correspondence should be addressed. E-mail: rechcalcium.chum{at}ssss.gouv.qc.ca.
Background: Non-(1-84) parathyroid hormone (PTH) fragments are large C-terminal fragments of PTH with a partially preserved N-terminal structure. They differ from other C-terminal PTH fragments, which do not have an N-terminal structure and do not react in intact (I) PTH assays. We aimed to identify the minimal N-terminal structure common to all non-(1-84) PTH fragments.
Methods: Sera obtained from six healthy individuals and six patients with primary hyperparathyroidism, and six serum pools from dialysis patients with different PTH concentrations were fractionated by HPLC and analyzed by four different PTH assays. Each assay was characterized by saturation analysis of its detection antibody and capacity to react with different PTH fragments. Human PTH(1-84) [hPTH(1-84)] calibrators were normalized to an in-house hPTH(1-84) calibrator.
Results: The cyclase activating PTH (CA-PTH) assay had an early (1, 2, ... ) epitope and reacted only with hPTH(1-84). The other assays had epitopes in region (13-34). Total (T) and intact (I) PTH assays had epitopes proximal to position 18 and reacted equally well with hPTH(1-84) and hPTH(7-84), and the Elecsys (E) PTH assay had an epitope distal to position 19, being saturable by hPTH(18-48) and also reacting with [Tyr34]hPTH(19-84). The HPLC profiles obtained with these assays showed that non-(1-84) PTH fragments did not react in the CA-PTH assay, as expected. The amount of non-(1-84) PTH detected by the other three assays was similar when the assay results were normalized to a common calibrator.
Conclusions: The results suggest that the amount of non-(1-84) PTH detected by epitopes proximal or distal to position 19 of the PTH structure is identical, indicating a common minimum structure starting before position 19. This in turn points to a probable high-affinity interaction with the C-PTH receptor, as observed previously with [Tyr34]hPTH(19-84) in various cell lines and in mouse osteocytes with PTH/PTHrP type I receptor ablation.
The following articles in journals at HighWire Press have cited this article:
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  H. Komaba, J. Shin, and M. Fukagawa Restoration of reversed whole PTH/intact PTH ratio and reduction in parathyroid gland vascularity during cinacalcet therapy for severe hyperparathyroidism in a uraemic patient Nephrol. Dial. Transplant., November 5, 2009; (2009) gfp578v1. [Abstract] [Full Text] [PDF]
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 R. Eastell, A. Arnold, M. L. Brandi, E. M. Brown, P. D'Amour, D. A. Hanley, D. S. Rao, M. R. Rubin, D. Goltzman, S. J. Silverberg, et al. Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 340 - 350. [Abstract] [Full Text] [PDF]
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 H. Komaba, Y. Takeda, J. Shin, R. Tanaka, T. Kakuta, Y. Tominaga, and M. Fukagawa Reversed whole PTH/intact PTH ratio as an indicator of marked parathyroid enlargement: five case studies and a literature review NDT Plus, August 1, 2008; 1(suppl_3): iii54 - iii58. [Abstract] [Full Text] [PDF]
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 M. R. Rubin, S. J. Silverberg, P. D'Amour, J.-H. Brossard, L. Rousseau, J. Sliney Jr, T. Cantor, and J. P. Bilezikian An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1 84) Is Overproduced in Parathyroid Carcinoma Clin. Chem., August 1, 2007; 53(8): 1470 - 1476. [Abstract] [Full Text] [PDF]
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T. Cantor, Z. Yang, N. Caraiani, and E. Ilamathi Lack of Comparability of Intact Parathyroid Hormone Measurements among Commercial Assays for End-Stage Renal Disease Patients: Implication for Treatment Decisions Clin. Chem., September 1, 2006; 52(9): 1771 - 1776. [Abstract] [Full Text] [PDF]
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 T. Arakawa, P. D'Amour, L. Rousseau, J.-H. Brossard, M. Sakai, H. Kasumoto, N. Igaki, T. Goto, T. Cantor, and M. Fukagawa Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 525 - 531. [Abstract] [Full Text] [PDF]
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P. D'Amour, A. Rakel, J.-H. Brossard, L. Rousseau, C. Albert, and T. Cantor Acute Regulation of Circulating Parathyroid Hormone (PTH) Molecular Forms by Calcium: Utility of PTH Fragments/PTH(1-84) Ratios Derived from Three Generations of PTH Assays J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 283 - 289. [Abstract] [Full Text] [PDF]
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