Uchiyama N, Yamamoto A, Kameda K, Yamaguchi H, Ito M
Department of Dermatology, Niigata University School of Medicine, Asahimachi-dori 1, 951-8510, Niigata, Japan.
J Dermatol Sci. 2000 Nov;24(2):134-41. doi: 10.1016/s0923-1811(00)00088-8.
The epidermal keratinocytes produce and secrete lipids to maintain the water barrier of the epidermis. To clarify the regulation of epidermal lipid synthesis, 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 the oxidation of NADPH, was slightly increased by hydrocortisone or testosterone, but not influenced by thyroid hormone, estrogen, progesterone or insulin. In immunohistochemical study of normal human epidermis, FAS was expressed strongly in the stratum granulosum and moderately in the uppermost layer of the stratum spinousum (SS), suggesting that fatty acid synthesis may increase during normal epidermal differentiation. In inflammatory disorders, such as psoriasis, lichen planus, and atopic dermatitis, FAS was also expressed in the lower SS and the stratum basale (SB), resulting in strong staining in the whole layers of the epidermis. Remarkable increase of FAS expression was only observed in the lower SS and the SB. Therefore, the activity of FAS in the epidermis may be regulated in the lower SS and the SB by local inflammation rather than by circulating hormones. In other components of the skin, FAS was strongly expressed not only in adipose tissue and sebaceous glands, which are known as active sites of lipid synthesis, but also in sweat glands, suggesting that the sweat glands can synthesize abundant fatty acids de novo.
表皮角质形成细胞产生并分泌脂质以维持表皮的水屏障。为阐明表皮脂质合成的调节机制，我们研究了激素对角质形成细胞脂肪酸合酶（FAS）活性以及人皮肤中FAS表达的影响。在培养的角质形成细胞中，通过测量NADPH的氧化来测定FAS活性，氢化可的松或睾酮可使其略有增加，但不受甲状腺激素、雌激素、孕酮或胰岛素的影响。在正常人表皮的免疫组织化学研究中，FAS在颗粒层中强烈表达，在棘层（SS）最上层中度表达，这表明在正常表皮分化过程中脂肪酸合成可能增加。在银屑病、扁平苔藓和特应性皮炎等炎症性疾病中，FAS也在SS下层和基底层（SB）表达，导致表皮全层染色强烈。仅在SS下层和SB中观察到FAS表达显著增加。因此，表皮中FAS的活性可能受局部炎症而非循环激素的调节，在SS下层和SB中发挥作用。在皮肤的其他成分中，FAS不仅在已知为脂质合成活跃部位的脂肪组织和皮脂腺中强烈表达，而且在汗腺中也强烈表达，这表明汗腺能够从头合成大量脂肪酸。
