Reversible inhibition by DMSO of hydrocortisone-induced keratinization of chick embryonic skin

Hydrocortisone, at a physiological concentration of 10^?8 M, induces keratinization of chick embryonic tarsometatarsal skin in a chemically defined medium in 4 days [1]. The presence of 1–4% DMSO with hydrocortisone reversibly prevented this keratinization. DMSO suppressed the appearance of epidermal structural protein, which was preferentially induced by hydrocortisone. It also suppressed hydrocortisone-induced epidermal transglutaminase activity; which was presumably responsible for polymerization and decrease in solubility of epidermal protein in keratinization, and it suppressed increase of epidermal protein. When DMSO was added to differentiated skin or added concomitantly with a higher concentration of hydrocortisone, epidermal transglutaminase activity was suppressed. Electron microscopic studies showed that hydrocortisone induced tonofilament bundles and keratinized cells with cellular envelopes, which are all characterestic of α-type keratinization of chick embryonic skin [2], and that DMSO inhibited hydrocortisone induced keratinization and kept the epidermis in an undifferentiated state. Moreover, DMSO inhibited epidermal DNA synthesis and increase in thickness of the epidermis during culture of hydrocortisone-treated skin, indicating that it suppressed cell proliferation as well as cell differentiation. DMSO by itself at 1 or 2 % did not affect epidermal cell differentiation, but suppressed cell proliferation when compared with untreated control.