Tumor-promoting phorbol esters induce metamorphosis and multiple head formation in the hydroid Hydractinia

Abstract. A pulse-type application of tumor-promoting phorbol esters (e.g., 12-tetra-decanoyl-phorbol-13-acetate, TPA) initiates the metamorphosis of planula larvae into polyps. Phorbol esters replace or bypass a lipophilic inducer which, in the natural habitat, is produced by environmental bacteria of the genus Alteromonos . In regeneration assays, isolated gastric regions of adult polyps were induced by TPA to form heads at both ends and often in the middle, too. TPA increases the "positional value," as does an endogenous, extractable factor X. The morphogenetic effectiveness of various phorbol esters is correlated with their tumor-promoting potency. These findings show that signaltransducing systems responding to phorbol esters are present even in basic metazoan animals. However, protein kinase-C activity could not be detected, and 1 -oleoyl-2-acetyl-glycerol could not replace TPA. On the other hand, the biological activity of phorbol esters is promoted by reducing the Mg²⁺ and increasing the K⁺ concentration of the external medium, and is strongly amplified by lithium or cesium. Thus, the existence of a more elementary, presumably cation-mediated transducing system is suggested.