Endogenous mediators of growth

Growth comprises three separate componcnts; whole-body growth, tissue turnover and repair, and last, the response to external stimuli. Whole-body growth can be divided into changes associated with muscle, skin, viscera and skeleton. Because of our interest in bone metabolism the present review will concentratc on the processes associated with skeletal growth, turnover, and response to external stimuli. Although some of the factors which will be discussed are specific to bone the majority affect other body tissues. There are too many endogenous mediators of growth to list in a review such as this. Basically such mediators can be divided into two groups (Table 1), those which have a systemic action such as growth hormonc (GH) and those which act locally such as the transforming growth factors (TGF). Of those systemic factors, some such as GH have a general effect on a number of tissues. However, there are also systemic factors such as gonadotropins and ACTH which have trophic actions on particular target organs. Endogenous mediators of growth are varied as well as numerous. For instance. calcium can be considcred a growth mediator for the parathyroid gland as prolonged hypocalcaemia results in a hypertrophy of the parathyroid gland. Bone growth and metabolism rely on the action of a number of factors affecting the proliferation and differentiation of the major bone cell types and modulating their activity. The skeleton serves a structural role, but it is also responsible for maintaining normocalcaemia. These two functions may occasionally bc contradictory but the primary role is the maintenance of serum Ca and at times of Ca stress (e.g. pregnancy and lactation) this occurs at the expense of skeletal integrity. Therefore, skeletal growth and metabolism are governed by two series of factors; those which control skeletal growth (e.g. G H and insulin-likc growth factor-1 (IGF-I)) and the calciotropic hormoncs (parathyroid hormone (PTH), calcitonin and 1,2.5-dihydroxycholecalciferol (1 ,25(OH)2D3)). It is becoming apparent that there is some overlap between these two systems as PTH, which at low levels is considered to be anabolic to the skeleton (Parsons et al. 1975), has recently been shown to increase the production of IGF-1 in bone cells (Canalis et a/. 1989; Linkhart & Mohan, 1989). The control of bone growth and metabolism is dependent on the activity and interactions of particular cell types. Thesc include the growth plate chondrocytes which are primarily responsible for longitudinal growth. The two cell types which are responsible for the turnover and repair of the skeleton are the osteoblasts which form bone and osteoclasts which resorb bone. This remodelling process is also important in intramembranous (skull growth) and endochondral bone formation during bone development and growth. The osteocyte, which is an osteoblast embedded in the matrix, is probably responsible for sensing the changes in mechanical demand (Pead et al. 1988).