Comparison of the effects of various lengths of synthetic human parathyroid hormone-related peptide (hPTHrP) of malignancy on bone resorption and formation in organ culture.
Parathyroid hormone-related peptide (PTHrP) has been shown to be the pathogenic agent in humoral hypercalcemia of malignancy (HHM), but the molecular forms that are secreted have not been fully characterized. PTHrP 1-34 has effects similar to parathyroid hormone (PTH), but C-terminal regions of the peptide, such as the 107-139 fragment found to inhibit resorption in a study by Fenton et al (1991), may have other biological activities not shared with PTH. We have compared the effects of the longer forms of recombinant human PTHrP (hPTHrP 1-84, 1-108, and 1-141) with hPTHrP 1-34 and synthetic bovine PTH (bPTH) 1-34 on bone resorption and formation in cultured neonatal mouse calvariae and fetal rat long bones. hPTHrP 1-84, 1-108, and 1-141 were qualitatively similar to hPTHrP 1-34 and PTH 1-34 in stimulating 45Ca release from both neonatal mouse calvariae and fetal rat long bones and in inhibiting the incorporation of [3H]-proline into collagenase digestible protein (CDP) and stimulating the incorporation of [3H]-thymidine (3H-TdR) in neonatal mouse calvariae. However, hPTHrP 1-108 and 1-141 were less potent at stimulating 45Ca release and inhibiting CDP labeling than hPTHrP 1-34, while hPTHrP 1-84 showed an intermediate potency. Since hPTHrP 1-108 and 1-141 were quite similar in potency, the difference cannot be attributed to an inhibitory effect of the 107-139 fragment. All the peptide lengths tested showed similar potency in stimulating [3H]-TdR incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)
Pilbeam
C C
CC
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Alander
C B
CB
Simmons
H A
HA
Raisz
L G
LG
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000187:drug effects*; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D051379:Mice; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C066078:parathyroid hormone-related protein (1-141); C054296:parathyroid hormone-related protein (1-34); C025076:parathyroid hormone (1-34), bovine; C066077:parathyroid hormone-related protein (1-84); C066079:parathyroid hormone-related protein (1-108); D003094:Collagen; D004247:DNA