Estrogenic activity of xenobiotics

Environmental contaminants, drugs and other xenobiotics have been found to affect both reproduction and developmental processes in various organisms. Exogenous compounds that mimic or inhibit the effects of endogenous hormones are known as endocrine disrupters. Recent studies have been focused mainly on mechanisms of action of estrogen-like compounds (xenoestrogens). Some synthetic steroid analogues, phytoestrogens, and many environmental pollutants such as metabolites of organochlorine pesticides, degradation products of surfactants, dialkyl phthalates, are considered to be the most important of them. The objective of this review has been to summarize the currently known mechanisms of action of endocrine disrupters and methods suitable for a detection of their effects. Recent studies show that the effects of xenoestrogens include interactions not only with the estrogen receptor (ER) pathway but also with other receptor systems. Beside the receptor-mediated effects, various other mechanisms exist that may modulate the endocrine system, including modulations of steroidogenesis and drug-metabolizing enzymes. A number of biochemical and cellular methods for the assesment of endocrine disrupters, allowing both the identification of individual chemicals as xenoestrogens and evaluation of their potential risk in the environment, are being developed and implemented. A combination of both in vitro and in vivo methods (e.g., recombinant receptor/reporter gene assays and detection of vitellogenin in plasma as well as the determination of activities of key steroidogenic and steroid-metabolizing enzymes) seems to be the most appropriate strategy.