chapter  7
32 Pages

Xenoestrogens and Estrogen Receptor Action

ByKenneth S. Korach, Vicki L. Davis, Sylvia W. Curtis, Wayne P. Bocchinfuso

Estrogens are a class of steroid hormones that influence development, sexual differentiation, fertility, and control of female reproductive tract organ respon­ siveness (50,74). Endogenous estrogens are formed by aromatization of andro­ gens by steroidogenic enzymes primarily in the gonads, as well as in extragonadal sites including the placenta, brain, and adipose tissue. In addition, a group of ex­ ogenous chemicals called xenoestrogens can display estrogen-like functions that influence the growth and development of female reproductive tissues. The source of xenoestrogens can be dietary in nature including phytoestrogens (eg, coumestrol, genistein), or exist as environmental pollutants (eg, o,p’-DDT, PCBs) pro­ duced as pesticides or waste from manufacturing processes. A noticeable feature of these estrogenic agents is their structural diversity (Fig. 1). Although a phe­ nolic ring is required for estrogen-like activity, the array of chemical structures and substitutions found in many environmental compounds make prediction of estrogenic potency difficult. Estrogen elicits its biologic actions in certain tissues by interacting with the estrogen receptor, which resides within the nucleus of tar­ get cells. Thus, xenoestrogens can interact with the estrogen receptor, inducing a response that mimics endogenous estrogen stimulation. Alternatively, the recep­ tor can bind the xenoestrogens, producing an inactive receptor-ligand complex that inhibits endogenous estrogen function. Either type of interference by xeno­ estrogens may result in aberrant reproductive function as a result of altered organ physiology or toxicity.