Direct Action of the Parathyroid Hormone-Like Human Hypercalcemic Factor on Bone

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-08, Vol.85 (15), p.5673-5677
• Main Authors: Thompson, David D., Seedor, J. Gregory, Fisher, John E., Rosenblatt, Michael, Rodan, Gideon A.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - pathology; Bones; Calcium; Calcium - blood; Cell Count; Diet; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Histology; Hormones. Regulation; Humans; Hypercalcemia; Hypercalcemia - chemically induced; Hypercalcemia - metabolism; Male; Neoplasm Proteins - pharmacology; Nephrocalcinosis - chemically induced; Nephrocalcinosis - pathology; Osteoclasts; Parathyroid Hormone - pharmacology; Parathyroid Hormone-Related Protein; Peptide Fragments - pharmacology; Phosphorus; Phosphorus - blood; Proteins; Rats; Rats, Inbred Strains; Thyroid. Parathyroid. Ultimobranchial body; Tibia - drug effects; Tibia - pathology; Tumors; Ungulates; Vertebrates: endocrinology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.15.5673

Peptides containing residues 1-34 of the human parathyroid hormone (PTH)-like hypercalcemic factor (hHCF), termed hHCF-(1-34)-NH2, produce effects similar to those of PTH in several biological systems in vitro and in vivo. However, there is conflicting evidence regarding the potency of hHCF on bone and, by implication, its role in calcium mobilization and the skeletal contribution to tumor-associated hypercalcemia. To resolve this conflict, the effects of infusing either hHCF-(1-34)-NH2or a peptide containing residues 1-34 of bovine PTH [bPTH-(1-34)] into unrestrained thyroparathyroidectomized rats on a low calcium diet were compared. Direct effects on bone histology and serum calcium levels, which are totally dependent on calcium mobilization from bone in these animals, were examined. bPTH-(1-34) and hHCF-(1-34)-NH2were equipotent in producing dose-dependent calcium mobilization from bone. At an infusion rate of 0.1 nmol/hr, both peptides produced hypercalcemia and extensive nephrocalcinosis. Histomorphometric analysis of tibiae from these animals after 48 hr of peptide infusion showed a dose-related increase in osteoclast number from 3-5 cells per mm2at 0.01 nmol/hr to ≈ 32 cells per mm2at 0.1 nmol/hr of hHCF or bovine PTH. These findings indicate that hHCF has a direct PTH-like effect on bone and, in this model system, the hHCF-(1-34)-NH2is equipotent to bPTH-(1-34).