Structural similarities of EDCs with endogenous hormones

The most outstanding characteristics of EDCs is the structural resemblance it has with body’s endogenous estrogenic and androgenic hormones, an ability to interact with hormone transport proteins, or an ability to disrupt hormone metabolism, these chemicals have the potential to mimic, or in some cases block, the effects of the endogenous hormone. This structural similarity aids in the endocrine disruption phenomena. The structural relationship is presented by showing the chemical structures of some endogenous sex steroid hormones and some potent EDCs.

Figure 1: Chemical structure of some environmental endocrine disruptors depicting structural similarity with endogenous hormones. The text in parenthesis with the name of each compound indicates their original source.

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The most frequently studied and best understood types of EDCs are those that imitate estrogens (Gillesby and Zacharewski, 1998; Kime, 1999).

Exposure of Fish

Both freshwater and marine fishes are exposed to a variety of EDCs from a range of sources. Effluents from industrial sites containing EDCs such as alkylphenol ethoxylates or bisphenol A, agricultural run-off which contains a number of endocrine disrupting pesticides and residues, sewage effluent, and sewage sludge dumped at sea, all result in the exposure of fish to EDCs.

The effects of EDCs on fishes include Egg-producing cells in the male testis Reduced testis growth rate and size Change in Behaviour and appearance Sex Reversal Increased liver size

Increased levels of vitellogenin (egg protein) in male fishes

Some of the most severe examples of endocrine disruption in fish have been found adjacent to sewage treatment plants. Effects are thought to be caused primarily by natural and synthetic estrogens and to a lesser extent by the degradation products of alkylphenol polyethoxylate surfactants. Effects found in fish near pulp and paper mills include reduced levels of estrogens and androgens as well as masculinization of females, which has been linked to the presence of β-sitosterol, a plant sterol. Effects seen in areas of heavy industrial activity typically include depressed levels of estrogens and androgens as well as reduced gonadal growth, which may be linked to the presence of PAHs, PCBs, and possibly dioxins. Pituitary-Hypothalamus-Gonadal Axis

One of the mainly studied pathways that can be affected by EDCs is the pituitaryhypothalamus-gonadal axis, which is used to illustrate the affects of EDCs on the endocrine system in fish. The release of gonadotropin releasing hormone (GnRH) from the hypothalamus in response to a series of environmental cues in fish results in the production and release of gonadotropin hormones (GTH) from the pituitary gland (Figure 2). The

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gonadotropins released into the systemic circulation elicit increased androgen and estrogen Production by the gonads.

Fig 2: Pituitary-hypothalamus-gonadal axis and the action of estradiol, Drean (1994).

The major estrogen in female fish, 17β-estradiol (E2), is produced primarily in the ovary by the follicular cells. In addition to their importance in eliciting reproductive behavior and the development and maintenance of secondary sex characteristics, the estrogens and androgens are involved in the production of gametes (Bone et al., 1995). In egg-laying fish, as in other egg-laying animals, the release of E2 from the ovary leads to the synthesis of large amounts of vitellogenin by the hepatocytes (liver cells). This high density lipoprotein, the precursor of egg yolk, is then transported from the liver via the circulatory system and incorporated into developing oocytes (Anderson et al., 1996). Although estrogens are typically associated with females and androgens with males, that demarcation may not be a rigid one (Sharpe, 1997). Research indicates that both male and female vertebrates produce and use estrogens and androgens. It is quite well accepted that a minor role for estrogens exists in males, in the regulation of GTH secretion by the pituitary gland. Exposure of an organism, however, to levels of natural hormones or EDCs which overwhelm or interfere with the proper functioning of the endocrine system has the potential to seriously affect the health of an organism and its progeny.

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Conclusion

Endocrine disruption has also been seen in areas of high industrial activity and chemical contamination. Although variable, effects typically include reduced levels of estrogens and inhibition of gonadal growth in female fish. More work is needed, however, to assess the effects of contaminants, particularly PAHs and PCBs on the endocrine system in male fish. Compounds thought responsible for observed effects include PCBs, PAHs and possibly dioxins.

Although endocrine disruption in fish has been documented in a number of field studies, little is currently known regarding the effect of EDCs at the population level. Several authors have noted that reproduction and population structure are almost certainly affected in areas where the greatest impacts on individual fish have been found, such as near certain Sewage Treatment Plants. To address this lack of information, the National Research Council has recommended long term studies of populations subjected to EDCs in order to assess effects on population size, age structure and dynamics.

As such more laboratory and field research is necessary to identify, detect the presence, and count the effects of EDCs, as well as develop strategies to reduce or even eliminate the discharge and effects of these compounds on fishes, wildlife and humanity as a whole.

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References

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5. Kime, D.E. 1998. Endocrine Disruption in Fish. Kluer Academic Publishers. Boston, MA 396pp.

6. Kime, D.E. 1999. A strategy for assessing the effects of xenobiotics on fish reproduction. Sci. Total Environ. 225: 3-11.

7. Gillesby, B.E., and T.R. Zacharewski. 1998. Exoestrogens: mechanisms of action and strategies for identification and assessment. Environ. Toxicol. Chem. 17(1):3-14. 8. Drean, Y.L., F. Pakdel, and Y. Valotaire. 1994. Structure and regulation of genes for estrogen receptors. In: Fish Physiology. ed. A.P. Farrell, and D.J. Randall, Volume XII, Chapter 11, p331-366. Academic Press, New York.

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