Peripheral metabolism of PTH (parathyroid hormone): Fate of biologically active amino terminus in vivo

Journal Article · Thu Dec 01 04:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:6036907

Bringhurst, R R; Stern, A M; Yotts, M; Mizrahi, N; Segre, G V; Potts, Jr, J T ^[1]

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1. Massachusetts General Hospital, Boston (USA)

Clearance of intact parathyroid hormone (PTH) from blood is associated with rapid uptake by liver and kidney, limited proteolysis by tissue endopeptidases and, within minutes, appearance of circulating carboxyl-(COOH)-terminal PTH fragments. The fate of the corresponding amino(NH{sub 2})-terminal portion of the hormone during this peripheral metabolism is still unknown, however. To determine this, the authors have employed ({sup 35}S)bovine PTH (bPTH) labeled to high specific activity at NH{sub 2}-terminal methionines, which permits direct monitoring of the fate of the PTH NH{sub 2}-terminus during metabolism in vivo. The ({sup 35}S)PTH was administered by bolus or continuous intravenous infusion to anesthetized normal rats, to rats subjected to acute ablation of the liver, the kidneys, or both, and to rats receiving co-infusions of excess synthetic bPTH(1-34) NH{sub 2}-terminal fragments. Analysis by high-resolution chromatographic techniques sensitive to 10{sup {minus}13} M ({sup 35}S)PTH peptides in plasma yields no evidence that peripheral metabolism of PTH generates circulating NH{sub 2}-terminal fragments, even when special measures are taken to block clearance of such putative fragments from blood. They find that the NH{sub 2}-terminus of PTH is rapidly degraded in situ by the liver but that both liver and especially kidney nevertheless contain low levels of NH{sub 2}-terminal PTH fragments that, although not released into the blood, are large enough to be potentially active. Thus the peripheral metabolism of PTH in normal animals does not normally lead to the formation of circulating amino terminal fragments of the hormone that might act independently of intact PTH on peripheral target tissues.

• OSTI ID: 6036907
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:6; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD-PLASMA CLEARANCE
BODY
CATTLE
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISTRIBUTION
DOMESTIC ANIMALS
EVEN-ODD NUCLEI
GLANDS
HORMONES
IN VIVO
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAMMALS
METABOLISM
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARATHORMONE
PEPTIDE HORMONES
PEPTIDES
PROTEINS
RADIOISOTOPES
RUMINANTS
SULFUR 35
SULFUR ISOTOPES
TISSUE DISTRIBUTION
VERTEBRATES