Bioactivity of parathyroid hormone and parathyroid hormone-like peptide: agonist and antagonist activities of amino-terminal fragments as assessed by the cytochemical bioassay and in situ biochemistry.
Parathyroid hormone-like peptide (PLP) is elaborated from certain tumors and is thought to play a role in the etiology of humoral hypercalcemia of malignancy. The amino-terminal portion of this peptide has a sequence homology with parathyroid hormone PTH. We have compared the agonist potency of the synthetic human amino-terminal 1-34 peptide [human (h)PLP-(1-34)] with that of intact PTH and its amino terminal fragment [hPTH-(1-34)] in the renal and metatarsal cytochemical bioassays (CBA). Furthermore, the antagonist activity of the truncated amino terminal molecule [hPLP-(3-34)] has been compared to that of [Norleu8.18,Tyr34]bovine PTH-(3-34)NH2, and we have also tested their ability to stimulate enzyme activities thought to be associated with bone formation and resorption. In the renal CBA, both PLP-(1-34) and hPTH-(1-34) were equipotent with intact hPTH. In the metatarsal CBA, although the two amino-terminal peptides were equipotent, they elicited an earlier response than the intact PTH molecule. In both assay systems the truncated PLP analog [hPLP-(3-34)] was a more potent antagonist of both PTH and PLP activity than was [Norleu8.18,Tyr34]bovine PTH-(1-34)NH2. In acute studies, hPLP-(1-34) and hPTH-(1-34) stimulated alkaline phosphatase and glucose 6-phosphate dehydrogenase activity in osteoblasts to a similar extent, and both peptides stimulated tartrate-resistant acid phosphatase and succinate dehydrogenase activity in osteoclasts. Longer exposure to the peptides resulted in stimulation of enzyme activity in osteoclasts but not osteoblasts, although there was no difference in potency between the two molecules.
Loveridge
N
N
Bone Growth and Metabolism Unit, Rowett Research Institute, Aberdeen, Scotland.
Dean
V
V
Goltzman
D
D
Hendy
G N
GN
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008682:Metatarsal Bones; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology; D010010:Osteoclasts / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism; D019379:Teriparatide
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); C067924:parathyroid hormone-related protein (3-34); D005954:Glucosephosphate Dehydrogenase; D013385:Succinate Dehydrogenase; D000469:Alkaline Phosphatase