We have demonstrated the net anabolic potential of a mid-region fragment of human
parathyroid hormone (hPTH), and a
protease resistant mutein derived from it, to stimulate growth of skeletal-derived tissues. The fragment
hPTH (28-48), lacking the N-terminal
amino acids necessary for stimulation of
adenylate cyclase, and therefore unable to stimulate
bone resorption by osteoclasts, was compared with the
protease-resistant double-mutein
hPTH (28-48) F34M L37T, full-length hPTH (1-84), the
protease resistant form hPTH (1-84) L37T, 17beta
estradiol (E(2)), and the combination of mid-region fragments of PTH and E(2). The
hormones, at concentrations spanning a 100-fold range, were given by 14
injections (6/week, excluding Saturday), to 17-day-old female Wistar-derived rats. At the low concentration of 200 ng/day of
PTH (1-84), or the molar equivalent of the fragment, and 50 ng E(2), all the
hormones increased significantly the specific activity of
creatine kinase (CK; a marker of skeletal cell proliferation) in tibial diaphysis and epiphysis, the width of the cortical bone in the humeral diaphysis, and the number of cells in the proliferating zone of the humeral epiphyseal growth plate. At a 10-fold lower concentration of both PTH and E(2), CK specific activity was synergistically stimulated in both diaphyseal bone and epiphyseal cartilage. However, PTH mid-region fragments at a dose of 1 microg/day did not increase trabecular bone volume.