Anabolic effects of estrogen and parathyroid hormone on skeletal tissues: the use of creatine kinase B activity as a response marker.

The rapid stimulation of the specific activity of the brain type isozyme of creatine kinase (CK BB) is an almost universal marker of cell stimulation. We have studied its stimulation in skeletal-derived cells and shown that the increase in its activity is closely correlated with the biochemical parameter of cell proliferation - [(3)thymidine incorporation into DNA - and with the morphological parameters of bone growth, increase in thickness of cortical bone and of the number of cells in the proliferating zone of the epiphyseal growth plate. We have used the increase in CK activity to demonstrate sex specific stimulation of diaphyseal bone, exclusively by estrogens in females and by androgens in males, and the dependence of sex steroid stimulation on an adequate level of vitamin D. After finding that parathyroid hormone can act as a mitogen via a phospholipase-C-phosphoinositide turnover pathway, we collaborated with colleagues at the GBF in Braunschweig to find that mid-region fragments of PTH could act exclusively as mitogens, without stimulating cAMP production leading to bone resorption. hPTH (28-48) variants designed to be resistant to proteolysis were efficient in stimulating CK specific activity in vitro and in vivo and increased cortical bone thickness and the number of proliferating epiphyseal cartilage cells in rat long bones. These results are put into an historical context and compared with recent studies, in this short, selective review.