TRANSFORMING GROWTH FACTOR-BETA-S - A MULTIFUNCTIONAL CYTOKINE FAMILY- IMPLICATION IN THE REGULATION OF ADRENOCORTICAL CELL ENDOCRINE FUNCTIONS

Knowledge of the structure of the first recognized transforming growth factor-beta (TGF-beta(1)) has led to the identification of more than two dozen structurally related peptides which appear of crucial import ance in the regulation of cell proliferation, cell differentiation and embryogenesis. TGF-beta(1) and its close homologs (TGF-beta(2-5)) are multifunctional peptides whose effects on cell functions are dependen t upon the cell type, the environment and the presence of other growth factors. TGF-beta(1) is produced and secreted as a latent macromolecu lar complex. One of the major steps in the control of TGF-beta activit y may thus be its release (activation) from its latent form upon the e ffect of local factors. Adrenocortical cells may be taken as an exampl e in which autocrine production of TGF-beta may be a component of a ne gative regulatory loop in balance with the positive effect of a system ic hormone (ACTH) in controlling the expression of the cell steroidoge nic differentiated functions. In this system, latent TGF-beta can be a ctivated by an ACTH-induced secreted protein (CISP), a member of the t hrombospondin family. This points to the importance of the functional interaction between TGF-beta s and extracellular matrix components in the local regulation of cell activities.