The (18-48)-fragment of human parathyroid hormone is a partial agonist for cAMP-dependent actions with retained mitogenic function.
In the search of PTH agonists, PTH fragments were examined for both cAMP-dependent and -independent actions on bone-derived assay systems. In a periosteal cell culture system from the embryonic chick, hPTH (18-48) was capable of inducing cell proliferation in a similar manner to hPTH (1-34) and hPTH (28-48) at picomolar concentrations, whereas hPTH (53-84) was inactive. Near physiological concentrations were needed for the proliferative action of PTH which seems to argue against a role for cAMP as a main mediator for growth response. In the tibiae organ culture system of embryonic chick cAMP stimulation and calcium mobilization requires micromolar concentrations. hPTH (18-48) produced, at a concentration of 10(-6) mol/L, a 14-fold increase in cAMP synthesis and an 11-fold increase in calcium mobilization and was 100-fold less active than hPTH (1-34). hPTH (28-48) and hPTH (53-84) had no significant effect. These results demonstrate that hPTH (18-48) retains the ability to induce cell proliferation and exhibits partial agonist activity in the cAMP/PKA signal transduction pathway.
Duvos
C
C
Gesellschaft für Biotechnologische Forschung mbH, Department of Gene Regulation and Differentiation, Braunschweig, Germany.
Scutt
A
A
Mayer
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D010521:Periosteum / Q000166:cytology / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013054:Spectrophotometry, Atomic; D013977:Tibia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C035453:parathyroid hormone (53-84); D004247:DNA; D000242:Cyclic AMP; D002118:Calcium