The activity of fatty acid synthase of epidermal keratinocytes is regulated in the lower stratum spinousum and the stratum basale by local inflammation rather than by circulating hormones

The epidermal keratinocytes produce and secrete lipids to maintain the wate r barrier of the epidermis. To clarify the regulation of epidermal lipid sy nthesis, we investigated the hormonal effect on the activity of fatty acid synthase (FAS) of the keratinocytes, and the expression of FAS in the human skin. In cultured keratinocytes, the FAS activity, assayed by measuring th e oxidation of NADPH, was slightly increased by hydrocortisone or testoster one, but not influenced by thyroid hormone, estrogen, progesterone or insul in. In immunohistochemical study of normal human epidermis, FAS was express ed strongly in the stratum granulosum and moderately in the uppermost layer of the stratum spinousum (SS), suggesting that fatty acid synthesis may in crease during normal epidermal differentiation. In inflammatory disorders, such as psoriasis, lichen planus, and atopic dermatitis, FAS was also expre ssed in the lower SS and the stratum basale (SB), resulting in strong stain ing in the whole layers of the epidermis. Remarkable increase of FAS expres sion was only observed in the lower SS and the SE. Therefore, the activity of FAS in the epidermis may be regulated in the lower SS and the SE by loca l inflammation rather than by circulating hormones. In other components of the skin, FAS was strongly expressed not only in adipose tissue and sebaceo us glands, which are known as active sites of lipid synthesis, but also in sweat glands, suggesting that the sweat glands can synthesize abundant fatt y acids de novo. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved .