Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat.
Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of (125)I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear (125)I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased. After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which (125)I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.
D000818:Animals; D002850:Chromatography, Gel; D003201:Computers; D006498:Hepatectomy; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology; D011863:Radioimmunoassay; D051381:Rats; D013997:Time Factors; D014511:Uremia / Q000378:metabolism*
D010281:Parathyroid Hormone; D010446:Peptide Fragments