Effects of endocrine disrupters on sex steroid synthesis and metabolism pathways in fish.
The interactions of estrogenic (nonylphenol, dicofol, atrazine), androgenic (organotins, phthalates, fenarimol) and anti-androgenic compounds (vinclozolin, diuron, p,p'-DDE) with key enzymatic activities involved in both synthesis and metabolism of sex hormones was investigated. Carp testicular microsomes incubated in the presence of androstenedione and different xenobiotics evidenced higher sensitivity of 5alpha-reductase activity than 17beta-hydroxysteroid dehydrogenase activity towards those chemicals. Dicofol, organotins and phthalates were among the most effective inhibitors. In contrast, ovarian synthesis of maturation-inducing hormones (20alpha- and 20beta-hydroxysteroid dehydrogenase activities) were enhanced by nonylphenol, dicofol, fenarimol and p,p'-DDE. Metabolic clearance pathways of hormones were also affected. Fenarimol, nonylphenol and triphenyltin inhibited the glucuronidation of testosterone and estradiol at concentrations as low as 10, 50 and 100 microM, respectively. Triphenyltin, tributyltin and nonylphenol were also inhibitors of estradiol sulfation with IC(50) values of 17, 18 and 41 microM. Overall, the data indicates the interaction of selected chemicals with key enzymatic pathways involved in both synthesis and metabolism of sex hormones. This interference might be one of the underlying mechanisms for the reported hormonal disrupting properties of the tested compounds, and might finally affect physiological processes such as gamete growth and maturation.
Thibaut
Rémi
R
Environmental Chemistry Department IIQAB-CSIC. C/Jordi Girona, 18, 08034 Barcelona, Spain. cpvqam@cid.csic.es
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D000735:Androstenedione / Q000494:pharmacology; D000818:Animals; D002347:Carps / Q000378:metabolism*; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D012724:Sex Attractants / Q000096:biosynthesis / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D015262:Xenobiotics / Q000494:pharmacology
D012724:Sex Attractants; D015262:Xenobiotics; D000735:Androstenedione; D014453:Glucuronosyltransferase; D015238:Sulfotransferases