Immunological evidences for the presence of small late carboxylterminal fragment(s) of human parathyroid hormone (PTH) in circulation in man.
Two antisera, C-52 and C-97, raised against bovine (b)PTH(1-84) in guinea pigs, were evaluated with 125I-[tyr53] human (h)PTH(53-84) as tracer and intact hPTH(1-84) and synthetic hPTH(39-84), representative of large carboxylterminal ("C") fragments found in circulation, as standards. In both assays, hPTH(39-84) was 5-6 times more potent than hPTH(1-84) on a molar basis in displacing the tracer. With both antisera, progressive deletion at the aminoterminal end of large "C" fragments, as in hPTH(53-84) and hPTH(65-84), lead to decreased immunoreactivity, hPTH(69-84) being non-immunoreactive. The mid-carboxylterminal fragments, hPTH(44-68) and hPTH(39-68), did not react in either assay. Each antiserum measured known quantities of pure hPTH(1-84) or hPTH(39-84) standards similarly. Serum PTH values obtained with antiserum C-97 were about 3 times higher in renal failure, 1.75 times higher in normal individuals and those with primary hyperparathyroidism, while similar to values measured with antiserum C-52 in individuals with secondary hyperparathyroidism without renal failure or with pseudohypoparathyroidism. When circulating PTH taken from patients with these disorders was fractionated by gel chromatography, both antisera recognized similar peaks of intact hPTH(1-84) and of large "C" fragments while antiserum C-97 further recognized a peak of smaller "C" fragments. This explained the different clinical behavior of the latter antiserum. Our findings demonstrate the existence of small late "C" fragments in circulation. They further suggest an influence of serum calcium and of renal function on the quantity of these fragments.
D'Amour
P
P
Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, Montréal, Québec, Canada.
Labelle
F
F
Wolde-Giorghis
R
R
Hamel
L
L
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002264:Carboxylic Acids; D002850:Chromatography, Gel; D006168:Guinea Pigs; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D010279:Parathyroid Diseases / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011863:Radioimmunoassay
D002264:Carboxylic Acids; D010281:Parathyroid Hormone; D010446:Peptide Fragments