Epidermal G1-chalone and transforming growth factor-beta are two different endogenous inhibitors of epidermal cell proliferation.

Epidermal G1-chalone and transforming growth factor-beta (TGF beta), two endogenous inhibitors of epidermal cell proliferation, were compared with regard to several effects on epidermis in vivo and in vitro. Both factors inhibited DNA labeling in a rat tongue epithelial cell line, with similar kinetics and half-maximal effects at approximately 1 pg/ml (enriched chalone) and 1 ng/ml (TGF beta). For primary neonatal mouse keratinocytes, TGF beta was found to be a rather strong inhibitor of cell proliferation, whereas chalone showed only a weak effect on cells grown in medium containing 1.2 mM Ca2+ and no effect at all in the presence of 0.06 mM Ca2+. Vice versa, upon i.p. injection, only chalone was able to inhibit mouse epidermal DNA synthesis in vivo, whereas TGF beta had no effect at all. A moderate increase of transglutaminase activity in neonatal primary mouse keratinocytes was induced by both factors at concentrations of about 300 pg TGF beta/ml and 10 pg chalone fraction/ml. Chalone did not compete with [125I]TGF beta for specific binding sites on primary murine keratinocytes. A polyclonal "chalone antiserum" did not interact with TGF beta, and a neutralizing TGF beta antibody that inhibited the effect of TGF beta on cell proliferation could not block the inhibitory effect of chalone on RTE2 cells. In contrast to TGF beta, epidermal G1-chalone did not induce proliferation of NIH-3T3 cells. These results indicate that epidermal G1-chalone and TGF beta are two different inhibitors of epidermal cell proliferation.