The (18-48)-fragment of human parathyroid hormone is a partial agonist for cAMP-dependent actions with retained mitogenic function.

Abstract

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.