Localization of de novo sterologenesis in mammalian skin.

Previous studies have demonstrated that the skin is an important site of de novo sterol synthesis and that there is a sex difference in cutaneous sterologenesis with male animals synthesizing more sterols than females. The aim of the present study was to localize the major sites of sterol synthesis within the skin and to determine which of these sites accounted for the sex differences in sterologenesis. In male and female rats whose dermal and epidermal layers are separated by dithiothreitol treatment, the dermis is the major site of skin sterologenesis (males 86% of total, females 82% of total). Moreover, the sex difference in skin sterol synthesis is quantitatively localized primarily within the dermal layer (approximately 2.5-fold greater in the dermis of males). Sterol synthesis is also increased in the epidermis of males. To rule out the possibility that sebaceous gland production accounted for our observations, we treated animals with isotretinoin (13-cis-retinoic acid), a drug that suppresses sebaceous gland sebum production. Sterol synthesis in the skin of both male and female rats is not significantly altered by isotretinoin administration and the sex difference in skin sterologenesis is unaffected. To further localize the sites of sterol synthesis within the skin, studies of hairless mice whose skin was split by DTT were initiated. In hairless mice, DTT separates the epidermis into upper (stratum corneum and granulosum) and lower (basal and spinous cells) strata. The basal layer was separated from the dermis by gentle scraping. As in rats, the dermis is the chief site of sterol synthesis in the skin. In addition, the lower layer of the epidermis (basal and spinous cells) is also a very active site of sterologenesis, accounting for 20% of total skin nonsaponifiable lipid synthesis. The upper epidermis accounted for only a small portion of total skin synthesis. It is highly likely that the bulk of cutaneous sterol synthesis occurs in the pilosebaceous epithelium.