Selective uptake of intact parathyroid hormone by the liver: differences between hepatic and renal uptake.

Abstract

A B S T R A C T Hepatic and renal extraction of immunoreactive parathyroid hormone (i-PTH) was studied in awake dogs with explanted kidneys and chronic indwelling hepatic vein catheters. After a single injection of bovine PTH 1-84 (b-PTH 1-84), hepatic arteriovenous (A-V) differences for immunoreactive PTH (i-PTH) was 39% at 2 min after injection but decreased to 0% by 25 min, despite high levels of i-PTH in the arterial circulation. Gel filtration of arterial and hepatic venous samples obtained when hepatic A-V differences for i-PTH were demonstrable revealed hepatic uptake of the intact hormone and addition of a smaller COOH-terminal fragment, eluting just after the intact hormone, to the hepatic venous blood. Gel filtration of samples obtained 20-30 min after injection of b-PTH 1-84 (when no hepatic A-V difference for i-PTH was demonstrable) revealed no detectable intact hormone in the circulation. Levels of COOH-terminal fragments of the hormone at the time were identical in arterial and hepatic venous samples. In additional experiments no hepatic A-V difference was observed after the injection of the synthetic bovine PTH 1-34 (syn b-PTH 1-34). By comparison there was a demonstrable A-V difference of 20% across the kidney for both intact PTH and COOH-terminal fragments that persisted until i-PTH disappeared from the circulation. The kidney also demonstrated an A-V difference of 22% after injection of syn b-PTH 1-34. These studies demonstrate selective extraction of intact PTH but not of its fragments by the liver. The kidney, on the other hand, extracted the intact hormone and both COOH and NHs terminal frag-

Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

“…In addition to the low calcium intake by these patients (27), another aspect to be considered is the possibility of increased PTH fragments detected by the second-generation PTH assays, which were used in the present study. The liver is an important site of peripheral PTH metabolism (28,29), but PTH clearance in chronic liver disease has not been determined.…”

Peripheral Metabolism of Intact Parathyroid Hormone

“…Circulating PTH has been shown to be a heterogenous mixture of intact hormone (PTH 1-84) and hormone fragments (1)(2)(3)(4)(5)(6)(7). In addition, work by several authors (3,(8)(9)(10)(11) has demonstrated different specificities among the target organs for the form of PTH that each organ removes from the circulation. For instance, several authors have demonstrated that intact PTH is removed from the circulation by the liver (3,4,8,9).…”

“…In addition, work by several authors (3,(8)(9)(10)(11) has demonstrated different specificities among the target organs for the form of PTH that each organ removes from the circulation. For instance, several authors have demonstrated that intact PTH is removed from the circulation by the liver (3,4,8,9). A previous report from our laboratory suggested that hepatic uptake of PTH is specific for intact PTH 1-84, whereas no hepatic uptake of carboxy terminal PTH fragments or synthetic b-PTH was demonstrable (9).…”

“…For instance, several authors have demonstrated that intact PTH is removed from the circulation by the liver (3,4,8,9). A previous report from our laboratory suggested that hepatic uptake of PTH is specific for intact PTH 1-84, whereas no hepatic uptake of carboxy terminal PTH fragments or synthetic b-PTH was demonstrable (9). In contrast, specific uptake mechanisms for the synthetic amino terminal fragment of PTH (syn b-PTH were demonstrated in the isolated perfused canine bone in vitro but only minor uptake rates ofintact hormone were demonstrable (11).…”

“…The metabolism of the hormone is thought to be rapid, judging from the rapid initial rates of disappearance of PTH following its addition to the circulation (1,3,15,16 (3,17). The liver has been identified as having the greatest uptake rate for intact hormone (3,9,17). Studies by D'Amour et al (17) suggest that most of hepatic PTH uptake is localized to Kupffer cells, and that hepatic cleavage of intact PTH and production of C-terminal fragments can be attributed to this cell type.…”