Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments.
We have found, in previous studies in vitro using skeletal derived cell cultures, that mid-region fragments of human parathyroid hormone (hPTH) stimulate [3H]thymidine incorporation into DNA and increase the specific activity of the brain-type isoenzyme of creatine kinase (CK). These changes occurred without an increase in cyclic AMP formation which is linked to bone resorption. In this study, we found that the mid-region fragment hPTH-(28-48) stimulated CK activity in diaphysis, epiphysis and kidney in a time- and dose-dependent manner, parallel to the effects of the whole molecule bovine (b)PTH-(1-84) and the fully active fragment hPTH-(1-34). The increase caused by hPTH-(28-48) at a dose of 1.25 micrograms/rat was not less than the 2-fold increase caused by a roughly equimolar concentration bPTH-(1-84). A significant increase was reached at 1 h after intraperitoneal injection in all cases. All three sequences of PTH caused an increase in [3H]thymidine incorporation into DNA in diaphysis and epiphysis, but not in kidney, 24 h after injection. A fragment further towards the C-terminal, hPTH-(34-47), was inactive compared with an equimolar concentration of the fragment hPTH-(25-39), which stimulated both CK activity and DNA synthesis. These results in vivo are in line with previous findings in vitro; they provide further support for the suggestion that mid-region fragments of the PTH molecule could be used to induce bone formation without incurring the deleterious effect of bone resorption.
Sömjen
D
D
Endocrine Unit, Ichilov Hospital, Faculty of Medicine, Tel Aviv University, Israel.
Schlüter
K D
KD
Wingender
E
E
Mayer
H
H
Kaye
A M
AM
D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects*; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances; D007668:Kidney / Q000201:enzymology; D010281:Parathyroid Hormone / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D006133:Growth Substances; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D004247:DNA; D003402:Creatine Kinase