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 isozy me of creatine kinase (CK BE) is an almost universal marker of cell st imulation. We have studied its stimulation in skeletal-derived cells a nd shown that the increase in its activity is closely correlated with the biochemical parameter of cell proliferation - [H-3]thymidine incor poration into DNA - and with the morphological parameters of bone grow th, 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 o f diaphyseal bone, exclusively by estrogens in females and by androgen s in males, and the dependence of sex steroid stimulation on an adequa te 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 th at mid-region fragments of PTH could act exclusively as mitogens, with out stimulating cAMP production leading to bone resorption. hPTH (28-4 8) variants designed to be resistant to proteolysis were efficient in stimulating CK specific activity in vitro and in vivo and increased co rtical bone thickness and the number of proliferating epiphyseal carti lage cells in rat long bones. These results are put into an historical context and compared with recent studies, in this short, selective re view. Copyright (C) 1997 Elsevier Science Ireland Ltd.