Comparison of the abilities of human parathyroid hormone(1-31)NH2 and human parathyroid hormone-related protein(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats.
N-terminal fragments of PTH and PTHrP, such as hPTH-(1-34) and hPTHrP-(1-34), are sufficiently similar with respect to amino acid sequence, location of functional domains, and higher order configuration to activate the same PTH/PTHrP receptor and the same two signal enzymes, adenylyl cyclase and phospholipase-Cbeta. Therefore, it was expected that hPTHrP-(1-31)NH2 would stimulate bone growth in ovariectomized rats as strongly as hPTH-(1-31)NH2. Like hPTH-(1-31)NH2, hPTHrP-(1-31)NH2 stimulated adenyly cyclase in ROS 17/2 osteosarcoma cells as strongly as the standard hPTH-(1-34) and like hPTH-(1-31)NH2, triggered a large drop in mean blood pressure when injected intravenously. Unlike hPTH-(1-31)NH2, however, hPTHrP-(1-31)NH2 could not stimulate trabecular growth in the distal femurs of young, sexually mature, ovariectomized rats.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario, Canada K1A OR6.
Morley
P
P
Willick
G E
GE
Ross
V
V
Langille
R
R
MacLean
S
S
Barbier
J
J
Isaacs
R J
RJ
Ohannessian-Barry
L
L
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C102836:parathyroid hormone (1-31)amide, human; D000262:Adenylyl Cyclases