Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays.
BACKGROUND
Recent evidence has shown that the assay for 'intact' parathyroid hormone (I-PTH) not only reacts with 1-84 PTH but also with large non-1-84 PTH fragments, most of which is probably 7-84 PTH. As a result, an assay specific for 1-84 PTH named 'whole' PTH (W-PTH) has been developed. The present study was designed: (i) to determine whether the W-PTH assay reliably measures PTH values in the dog; (ii) to evaluate differences between the W-PTH and I-PTH assays during hypo- and hypercalcaemia; and (iii) to assess the peripheral metabolism of W-PTH and I-PTH.


METHODS
In normal dogs, hypocalcaemia was induced by EDTA infusion and was followed with a 90 min hypocalcaemic clamp. Hypercalcaemia was induced with a calcium infusion.


RESULTS
I-PTH and W-PTH values increased from 36+/-8 and 13+/-3 pg/ml (P=0.01) at baseline to a maximum of 158+/-40 and 62+/-15 pg/ml (P=0.02 vs I-PTH) during hypocalcaemia. The W-PTH/I-PTH ratio, 38+/-4% at baseline, did not change during the induction of hypocalcaemia, but sustained hypocalcaemia increased (P<0.05) this ratio. During hypercalcaemia, maximal suppression for I-PTH was 2.0+/-0.5 and only 5.7+/-0.6 pg/ml for W-PTH, due to a decreased sensitivity of the W-PTH assay at values <5 pg/ml. The disappearance rate of PTH was determined in five additional dogs which underwent a parathyroidectomy (PTX). At 2.5 min after PTX, W-PTH was metabolized more rapidly, with a value of 25+/-2% of the pre-PTX value vs 30+/-3% for I-PTH (P<0.05).


CONCLUSIONS
(i) The W-PTH/I-PTH ratio is less in the normal dog than in the normal human, suggesting that the percentage of non-1-84 PTH measured with the I-PTH assay is greater in normal dogs than in normal humans; (ii) the lack of change in the W-PTH/I-PTH ratio during acute hypocalcaemia is different from the situation observed in humans; and (iii) the dog appears to be a good model to study I-PTH and W-PTH assays during hypocalcaemia.
Department of Medicina y Cirugia Animal, Universidad de Cordoba, Campus Rabanales, Ctra Madrid-Cadiz km 396, 14014 Cordoba, Spain.
Jose C
JC
Estepa
Ignacio
I
Lopez
Arnold J
AJ
Felsenfeld
Ping
P
Gao
Tom
T
Cantor
Mariano
M
Rodríguez
Escolastico
E
Aguilera-Tejero
D000818:Animals; D002122:Calcium Chloride; D004195:Disease Models, Animal; D004285:Dogs; D004492:Edetic Acid; D005260:Female; D006934:Hypercalcemia / Q000139:chemically induced / Q000378:metabolism*; D006996:Hypocalcemia / Q000139:chemically induced / Q000378:metabolism*; D015592:Immunoradiometric Assay; D007262:Infusions, Intravenous; D007668:Kidney / Q000502:physiology; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D004492:Edetic Acid; D002122:Calcium Chloride