Drug-induced alterations in rat peritubular cell cytoskeleton result in proteoglycan synthesis modifications. Comparison with some intracellular signaling pathways

The influence of phorbol myristate acetate (PMA), dibutyryl cAMP and insuli n-like growth factor (IGF-1) as well as cytoskeletal disrupting drugs on mo rphological changes has been studied in peritubular cells isolated from imm ature rat testis. Morphological studies were combined with immunofluorescen ce investigations of cytoskeletal elements and their rearrangements by vari ous agents. The results were correlated with modulation of proteoglycan syn thesis. Peritubular cells exposed to dibutyryl cAMP or cytochalasin D were transformed from flattened, fibroblast-like into neuronal-like morphology. In such cells, destruction of actin filaments was accompanied with a 50% de crease in cell-associated proteoglycan synthesis as well as with oversulfat ion of total proteoglycans. On the contrary, peritubular cell shape has bee n slightly altered after addition of PMA, IGF-1, vinblastine or colchicine. After these treatments, destruction or rearrangement of cytoskeletal eleme nts was observed; cell-layer proteoglycan synthesis remained either unchang ed or increased while total proteoglycans were always undersulfated. IGF-1, PMA and dibutyryl cAMP modified the peritubular cell morphology, cytoskele tal organization and proteoglycan production; the cytoskeleton disrupting d rugs such as vinblastine, colchicine and cytochalasin D mimicked some of th ese effects. These observations suggest that alterations in proteoglycan bi osynthesis, after activation of tyrosine kinase, protein kinase C and prote in kinase A pathways might be mediated, at least in part, by the disorganiz ation of the cytoskeleton structure. (C) Elsevier, Paris.