Endogenous mediators of growth

In the present review it is not possible to discuss the effects of the numerous endogenous mediators of growth. What we have attempted to do is to indicate the areas of controversy and the need for further research. In our view, four main questions arise. First, what are the relative contributions of the direct and indirect effects of GH? Indeed, if GH can produce all its effects by local production of IGF, is the original somatomedin hypothesis still tenable? Second, how is the biological activity of the IGF modified by the presence of binding proteins? Because of the role of binding proteins in modulating IGF bioactivity, care must be taken when interpreting results from immunoassays for IGF because this will only represent the concentration of IGF not the level of biological activity, a situation which is analogous to that which pertains with certain polypeptide hormones (for review, see Robertson et al. 1987). Third, how are the activities of the osteoblast and osteoclast coupled so that in the mature adult, bone formation and bone resorption are roughly equivalent? Understanding of this process will undoubtedly involve the elucidation of the roles and interactions between a number of locally acting growth factors and systemic hormones and will lead to the understanding of certain metabolic bone diseases such as osteoporosis. Last, how is the response to local stimuli such as mechanical stress transduced? This is again probably dependent on the activity of local growth factors but may also involve changes in the interactions between bone cells and their underlying matrix components (Skerry et al. 1988).