Metabolism of bovine parathyroid hormone. Immunological and biological characteristics of fragments generated by liver perfusion.

Abstract

A B S T R A C r The metabolism of bovine parathyroid hormone (PTH) by the perfused rat liver was studied. Labeled hormone, with or without cold hormone, was infused into the circulating perfusion medium containing various calcium concentrations. Perfusate samples at various time periods after the introduction of PTH into the system were chromatographed on Bio-gel P-10; radioactivity and/or immunoreactivity were measured in eluted fractions.Before the perfusion, all immuno-and radioactivity eluted in a single peak, with an apparent mol wt of 9,500 (peak I). After perfusion for 15 min, two other peaks with approximate mol wt of 7,000 (peak II) and 3,500 (peak III) were discernible. Peak I contained both NH2-terminal and COOH-terminal immunoreactivity and was biologically active at all time periods tested. The relative contribution of NH2-terminal and COOH-terminal immunoreactivity to the total immunoreactivity remained constant in this peak throughout the perfusion. In every respect, peak I had the characteristics of intact hormone. At all times, peak II consisted of only COOH-terminal immunoreactivity and was biologically inactive. At early time periods, peak III contained predominantly NH2-terminal immunoreactivity and was biologically active. With time, the relative contribution of NH2-terminal immunoreactivity decreased strikingly while that of COOH-terminal immunoreac-

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

“…Thus, under conditions of constant delivery of intact b-PTH 1-84, the liver demonstrates constant extraction that rapidly disappears upon termination of the infusion. DISCUSSION Degradation of PTH has been demonstrated in studies in vitro using saline extracts of porcine liver (24) and the isolated perfused rat liver (12). The latter studies demonstrated production of PTH fragments by the liver when it was perfused with either tritiated or unlabeled b-PTH 1-84.…”

“…A prolonged disappearance time of injected radiolabeled 'I-PTH has been demonstrated in partially hepatectomized rats (15). Studies in vitro have demonstrated progressive degradation of the intact hormone and release of hormonal fragments into the perfusion medium by the isolated perfused rat liver (12). The fragments produced included a large COOH-terminal fragment wiith an estimated mol wt of 7,000 that appeared to be secondarily degraded to a COOH-terminal fragment, approximate mol wt 3,500.…”

Inhibition of Parathyroid Hormone Secretion by 25-Hydroxycholecalciferol and 24,25-Dihydroxycholecalciferol in the Dog

“…This antiserumil cross-reacts with intact hormone as well as NH2-and COOH-ternuinal fragments (21)(22)(23). For phase separations, the dextrani-coated charcoal method as described by Arnaud et al was used (24).…”

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

“…Bovine 1-84 was less effective after parathyroid hormone, which primarily reaches the liver the liver and, to a more via the systemic arterial circulation, is specifically perfusate. This tempera-cleaved by perfused rat liver to parathyroid hormone suggests that tempera-fragments that are biologically active and resemble cesses, binding interac-those seen in the peripheral blood (39 From a teleologic viewpoint, the liver probably serves as a major site for inactivation, by degradative catabolism, of somatostatin. The liver has a strategic anatomic location between the somatostatin-rich gut and pancreas and the systemic circulation, into which the unrestricted entry of active somatostatin from the gastrointestinal tract might have excessive ubiquitous effects.…”