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ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE
Gray Jr., L E., V S. Wilson, T E. Stoker, C R. Lambright, J. R. FURR, N. C. NORIEGA, P. C. HARTIG, M. C. CARDON, M. B. ROSEN, G. T. ANKLEY, A. K. HOTCHKISS, E. F. ORLANDO, L. J. GUILLETTE JR., AND W. R. KELCE. ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE. 2nd EditionChapter 2-2, R.Naz (ed.), Endocrine Disruptors. CRC Press LLC, Boca Raton, FL, , 313-345, (2004).
To discuss environmental chemicals that display antiandrogenic or androgenic activity
Within the last ten years, awareness has grown about environmental chemicals that display antiandrogenic or androgenic activity. While studies in the early 1990s focused on pesticides that acted as androgen receptor (AR) antagonists, it soon became evident that this was not the only endocrine mode of action by which man-made chemicals could disrupt the androgen signaling pathway. Several classes of antiandrogenic toxicants have been shown to act as AR antagonists, while others inhibit Leydig cell testosterone production; other pesticides display dual EDC mechanisms of action, being AR antagonists and inhibitors of testosterone synthesis. Recently, we learned that toxicants can also alter sexual differentiation by inhibiting insl3 mRNA production during sexual differentiation.
The classes of chemicals known to interfere with the androgen signaling pathway include dicarboximide fungicides (i.e. vinclozolin), organochlorine based insecticides (p,p' DDT and DDE), conazole fungicides (prochloraz), plasticizers (phthalates), and urea-based herbicides (linuron). In utero exposure to these "antiandrogenic" chemicals results in profiles of effects in the offspring that are pathognomonic for each mode of action. Mixture studies reveal that these chemicals generally induce cumulative dose-additive responses when co-administered with one another.
Although we have known about estrogen-mimics for decades, androgens of anthropogenic origin were only found in the environment in 2001. Recent studies from several laboratories around the world reported that effluents from pulp and paper mills display androgenic activity, often of sufficient potency to masculinize and/or sex-reverse female fish. Within the last year or two we also have learned that effluent from beef cattle feedlots was androgenic and may contain 17 beta trenbolone, a steroid used to promote growth in cattle. In summary, we are only beginning to understand what classes of chemicals have the potential to act as EDC's by altering the androgen signaling pathway. Although we have little data from field studies on the effects of these chemicals or their levels in the environment, animal studies demonstrate that antiandrogens have the potential to alter male sexual differentiation and reproductive development whereas the androgenic substances can masculinize and defeminize females.