Synthetic parathyroid hormone-like protein (1?74) is anabolic for bone in vivo
Autor: | Eleanor C. Weir, Karl L. Insogna, Gordon A. Terwilliger, Leanordo Sartori |
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Rok vydání: | 1992 |
Předmět: |
Male
medicine.medical_specialty Anabolism Injections Subcutaneous Endocrinology Diabetes and Metabolism chemistry.chemical_element Parathyroid hormone Calcium Bone and Bones Phosphates Rats Sprague-Dawley Hydroxyproline chemistry.chemical_compound Endocrinology Calcitriol In vivo Teriparatide Internal medicine medicine Animals Orthopedics and Sports Medicine Dose-Response Relationship Drug Parathyroid hormone-related protein Catabolism Body Weight Parathyroid Hormone-Related Protein Proteins Hormones Peptide Fragments Rats chemistry Parathyroid Hormone hormones hormone substitutes and hormone antagonists medicine.drug |
Zdroj: | Calcified Tissue International. 51:30-34 |
ISSN: | 1432-0827 0171-967X |
Popis: | Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1–34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1–34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1–74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1–74) (1 and 2 nmol/100 g body weight, bw), bPTH(1–34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxypro-line content. Results of these studies indicate that PTHRP (1–74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period. |
Databáze: | OpenAIRE |
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