Proc. West. Pharmacol. Soc. 48: 129-133 (2005) 129 Effects of Single Administration of Diethylstilbestrol on Murine Langerhans Cells Ana Martha Hernandez-Segura 1 , Isai Ayala-Garcia 1 , S. Judith Alvarez-Pérez 2 , Andres E. Castell-Rodriguez 2 Beatriz Hernandez-Tellez 2 , Juan Jose Mandoki 3 and Maria Dolores Ramirez-Gonzalez 3 1 Fourth Year Medical Students; Departments of 2 Cell and Tissue Biology and 3 Pharmacology. School of Medicine, National Autonomous University of Mexico *Email: mdrg@servidor.unam.mx ABSTRACT Diethylstilbestrol (DES) is a synthetic compound with potent estrogenic actions useful in the treatment of prostate carcinoma despite the fact that it can also induce some forms of neoplasia. Both effects are thought to be related to its estrogenic actions and very little attention has been focused on the possible effect of DES on the immune response. Skin is the largest organ of the body and constitutes the first line of defense against xenobiotics. The Skin Immune System (SIS) has become the center of attention of research for the development of new therapeutic approaches for neoplasic diseases. Langerhans cells (LC), as an element of SIS, are “professional” antigen presenting cells resident in the skin that participate in the immune response associated with tolerance and acquired immunity to antigens. Hence in this work we studied the effect of DES on LC of murine skin as a model to analyze the possible effect of DES on the immune response. Male CD-1 mice (20 to 35 g body weight) were treated topically (TO) or subcutaneously (SC) with DES (10 and 100 mg/kg, dissolved in ethanol) and sacrificed at 12, 84 and 228 hr. LC were quantified in the ear skin of mice using both an enzymatic histochemical technique to demonstrate ATP-ase activity; and an indirect immuno- histochemical assay for detecting class II molecules of the major histocompatibility complex (MHC-II). DES induced a significant time- and dose- dependent reduction in the number of LC (P<0.05). Data presented here suggest that estrogens may exert a modulatory action on LC. INTRODUCTION Skin is the largest organ in the body and it constitutes the first line of defense against infectious agents and xenobiotics. Langerhans Cells (LC) are specialized dendritic cells of bone marrow origin that migrate from the skin to the lymph nodes and have been implicated in the phatogenesis and phatophysiology of diverse diseases (see review in this volume). LC have attracted attention as targets for drug action and drug development in as much as they appear to operate as the sentinels of the SIS [1]. Recent reports have shed light on the role of estrogens in the modulation of lymphocyte survival and expansion, and on the mechanisms by which estrogen can activate immune cells via multiple signaling and genomic pathways [2]. Diethylstilbestrol (DES) was the first synthetic estrogen useful for oral administration. It was synthesized in 1938 and was widely prescribed in the United States from the early 1940’s until 1970’s. It was primarily used as treatment for preventing miscarriages or premature deliveries [3]. However, in 1971 a bulletin issued by the U.S. Food and Drug Administration warned physicians to stop prescribing DES to pregnant women because of its link to a rare form of vaginal cancer (clear-cell adenocarcinoma) in the daughters of DES – treated patients [3]. Other indications like hormone replacement therapy, control of menstrual disorders, relief or prevention of postpartum breast engorgement, palliative therapy for cancer of the prostate in men, breast cancer in postmenopausal women, and as a postcoital contraceptive continued into the early 1980’s. Large doses of DES are required for effective treatment of advanced prostate cancer and breast cancer [4], but due to the cardiovascular toxicity observed, these indications are obsolete [5]. Since its appearance, DES also gained significant applications in veterinary medicine as a growth promoter in cattle, sheep, and poultry either as a food supplement or subcutaneous implants [6]. However the prohibition for its use in food - producing animals was issued in 1979, and its use is of debatable advantage in veterinary medicine [7]. Therapeutic and toxic effects produced by DES are thought to be related to its estrogenic properties and very little attention has focused on its possible effect on the immune system [2]. In this work we studied the effect of DES on LC recognizing that these dendritic cells function as the sentinels of the SIS [1].