Endocrine disruptors in the marine environment: mechanisms of toxicity and their influence on reproductive processes in fish.
Recent research demonstrated how endocrine-disrupting chemicals (EDCs) may disturb wildlife populations and possibly also represent a human health risk. Much of the focus has been on (anti-)estrogenic and (anti-)androgenic effects, and these effects are thought to be mediated through the estrogen (ER) and androgen (AR) receptors, respectively. The seriousness of the problem has led international bodies such as the Organization for Economic Cooperation and Development (OECD) and the European Union (EU) to initiate large research programs and developments toward new guidelines and regulations. EDCs have both synthetic and natural sources. The mechanisms of action of EDCs can be divided into: (1) agonistic/antagonistic effect ("hormone mimics"), (2) disruption of production, transport, metabolism, or secretion of natural hormones, and (3) disruption of production and/or function of hormone receptors. However, the number of nuclear hormone receptors being potential targets for EDCs has increased dramatically the last decade, opening up new avenues for possible endocrine disruptor effects. In studies with Atlantic salmon, data showed that 4-nonylphenol, a model xenoestrogen previously used in large volumes, for example, in paints and detergents, acts as an estrogen mimic, as a steroid metabolism disruptor, and by modulating estrogen receptor (ER) levels, indicating that one single compound exerts all of these three mechanisms, depending on the dose given to the organism. A hypothesis explaining this observation is that the nature of the effect of an EDC is determined by dose-dependent routing and cross-talk between different classes of nuclear receptors.
Goksøyr
Anders
A
Department of Molecular Biology, University of Bergen, and Biosense Laboratories AS, Bergen, Norway. anders.goksoyr@mbi.uib.no
D000818:Animals; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D004527:Egg Proteins / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D020847:Estrogen Receptor Modulators / Q000633:toxicity; D005399:Fishes; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D015415:Biomarkers; D004527:Egg Proteins; D052244:Endocrine Disruptors; D020847:Estrogen Receptor Modulators; D018160:Receptors, Cytoplasmic and Nuclear; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; C423083:zona radiata protein, fish