The effects of testosterone on skin barrier

Background: Although there are no known gender-related differences in permeability barrier function in adults, estrogen accelerates whereas testosterone retards barrier develop-ment 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.