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.
BACKGROUND
The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical.


OBJECTIVE
The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH.


METHODS
CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure.


RESULTS
From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84).


CONCLUSIONS
PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.
D'Amour
Pierre
P
Centre de Recherche, Centre Hospitalier de l'Université de Montréal-Hôpital Saint-Luc, Montréal (Québec), Canada H2X 1P1. rechcalcium.chum@ssss.gouv.qc.ca
Räkel
Agnès
A
Brossard
Jean-Hugues
JH
Rousseau
Louise
L
Albert
Caroline
C
Cantor
Tom
T
D000328:Adult; D000465:Algorithms; D002118:Calcium / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000494:pharmacology; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood; D006996:Hypocalcemia / Q000097:blood; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D000077559:Sodium Citrate
D002951:Citrates; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D000077559:Sodium Citrate; D002122:Calcium Chloride; D002118:Calcium