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.