ENVIRONMENTAL ANTIANDROGENS - DEVELOPMENTAL EFFECTS, MOLECULAR MECHANISMS, AND CLINICAL IMPLICATIONS

Industrial chemicals and environmental pollutants can disrupt reproduc tive development in wildlife and humans by mimicking or inhibiting the action of the gonadal steroid hormones, estradiol and testosterone. T he toxicity of these so-called environmental endocrine disrupters is e specially insidious during sex differentiation and development due to the crucial role of gonadal steroid hormones in regulating these proce sses. This review describes the mechanism of toxicity and clinical imp lications of a new class of environmental chemicals that inhibit andro gen-mediated sex development. For several of these chemicals, includin g the agricultural fungicide vinclozolin and the ubiquitous and persis tent 1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane metabolite, 1,1-di chloro-2,2-bis(p-chlorophenyl) ethylene, the molecular mechanism of ac tion and the adverse developmental effects on male sex differentiation have been elucidated and are used as examples. Environmental chemical s with antiandrogenic activity offer profound implications with regard to recent clinical observations that suggest an increasing incidence of human male genital tract malformations, male infertility, and femal e breast cancer. Finally, in light of increasing concern over the pote ntial endocrine disrupting effects of environmental pollutants, an in vitro/in vivo investigational strategy is presented which has proved u seful in identifying chemicals with antiandrogen activity and their me chanism of action.