BACKGROUND: Although there are no known gender-related differences in permeability barrier function in adults, estrogen accelerates whereas testosterone retards barrier development in fetal skin. However, there have been few studies concerning the effects of testosterone on the skin barrier. OBJECT: We evaluated the effects and mechanisms of testosterone on the skin barrier. METHODS: In this experiment, hairless mice were divided into three groups; sham-operated, castrated and testosterone-replacement castrated group. Testosterone was administered subcutaneously once a day for 7 days. We performed a skin biopsy at 7 days and performed hematoxyline-eosin staining, calcium-ion capture cytometry and the immunohistochemical examination of involucrin, loricrin, filaggrin and proliferating cell nuclear antigen (PCNA). The specimens were prepared for electron microscopy using RuO4 and OsO4 postfixation. RESULTS: The results were summarized as follows 1. Light microscopic findings of the testosterone-replacement castrated group showed apparent hyperkeratosis and acanthosis, not present in the sham-operated and castrated group. 2. Whereas the expression of involucrin, loricrin and filaggrin of immunohistochemical staining and in situ hybridization of the sham-operated and castrated group were normal, it was abnormal in the testosterone-replacement castrated group. 3. Labelling indices for PCNA in the sham-operated and castrated group were not statistically different, but the testosterone-replacement castrated group showed a marked increase of PCNA labeling index. 4. Wherease the calcium gradient was normal in the sham-operated and castrated group, it was distorted in the testosterone-replacement castrated group. Calcium deposition was increased through all layers of the epidermis and the calcium gradient disappeared in the testosterone-replacement castrated group. 5. Normal looking membrane structure was observed in the sham-operated and castrated group, but a membrane structure which appeared fragmented, incomplete lipid bilayer structures and prominent dilatation of lacunar domains were observed only in the testosterone-replacement castrated group. CONCLUSION: From the above results, it is concluded that there is a functional alteration of the epidermal barrier induced by testosterone, including the formation of an abnormal cornified envelope and also incomplete lipid synthesis.
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