AJP - Endocrinology and Metabolism, Vol 246, Issue 3 249-E255, Copyright © 1984 by American Physiological Society
Evidence of two forms of hepatic extraction of parathyroid hormone in dogs in vivo
P. D'Amour and P. M. Huet
The fractional hepatic extraction (FHE) of oxidized 125iodine-labeled
bovine parathyroid hormone, 125I-bPTH-(1-84), is dependent on the integrity
of the 28-48 sequence of the bPTH structure. A second type of FHE, related
to the biologically active core of the hormone, is suggested by liver
adenylate cyclase activation or cAMP production by bPTH-(1-84) or
bPTH-(1-34). We have thus compared the FHE of biologically active
bPTH-(1-84), bPTH-(1-34), and of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide
with that of oxidized 125I-bPTH-(1-84). The preparations, together with
reference substances, were injected into the portal vein of anesthetized
dogs and dilution curves obtained by counting the radioactivity or assaying
the immunoreactivity present in hepatic vein samples. FHE was calculated
from these curves. Results were validated by gel chromatography analysis of
the 125I-radioactive or immunoreactive preparation injected and recovered.
In six dogs, the FHE of bPTH-(1-84) was 59.9 +/- 8.9%, 23% higher than the
value of 39.6 +/- 9.3% obtained for 125I-bPTH-(1-84) injected
simultaneously (P less than 0.0005). This difference was similar to the FHE
of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide (16.4 +/- 7.2%) and
bPTH-(1-34) (23.5 +/- 10.4%) measured in seven dogs. Analysis of the
various gel chromatography profiles revealed that the entire FHE process
could be explained by extraction of the appropriate peak of each
preparation; a small amount of fragment was also generated across the liver
in the case of bPTH-(1-84) (1.6%) and 125I-[Nle8, Nle18, Tyr34]-bPTH-(1-34)
amide (2.8%), with a larger quantity in the case of bPTH-(1-34)
(17%).(ABSTRACT TRUNCATED AT 250 WORDS)
