Programmed expression of cholesterol sulfotransferase and transglutaminase during epidermal differentiation of murine skin development.

To clarify the role of cholesterol sulfate (CS) in the process of epidermal differentiation in vivo, we investigated the concentration of CS and the specific activities of cholesterol sulfotransferase (CST), cholesterol sulfate sulfatase (CS sulfatase) and epidermal transglutaminase (ETG) in murine skin in the pre- and postnatal periods. In the skin at day 14 of gestation, CS was not detected with TLC and the specific activities of all the enzymes were low. However, concomitant with the formation of the multilayered structure of the epidermis (at day 16), the specific activities of CST steeply increased. Although the insoluble CS sulfatase in the microsomal fraction remained at a relatively constant level, the soluble CST in the cytosol fraction showed a 6-fold increase from day 14 to day 16, and the activity decreased continuously in the following period, reaching one forty-sixth of the maximum level at 4-months-old mice. Reflected by the increase in activity, CS was detected in fetal skin at day 15, and the concentration in epidermis significantly increased during the gestation period, reaching maximum level at day 17. Furthermore, the changes in the concentration of cholesterol sulfate were identical with those of N-(O-linoleoyl)-omega-hydroxy fatty acyl sphingosine and its glucosyl derivative in the epidermis. On the other hand, the specific activity of ETG increased after birth. Thus, the activation of CST and ETG was shown to occur separately in association with the formation of the multilayered structure and thickening of the stratum corneum, respectively.