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 micr...

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Veröffentlicht in:The Journal of steroid biochemistry and molecular biology 2004-12, Vol.92 (5), p.485-494
Hauptverfasser: Thibaut, Rémi, Porte, Cinta
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container_title The Journal of steroid biochemistry and molecular biology
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Porte, Cinta
description 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 5α-reductase activity than 17β-hydroxysteroid dehydrogenase activity towards those chemicals. Dicofol, organotins and phthalates were among the most effective inhibitors. In contrast, ovarian synthesis of maturation-inducing hormones (20α- and 20β-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 μM, respectively. Triphenyltin, tributyltin and nonylphenol were also inhibitors of estradiol sulfation with IC 50 values of 17, 18 and 41 μM. 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.
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Carp testicular microsomes incubated in the presence of androstenedione and different xenobiotics evidenced higher sensitivity of 5α-reductase activity than 17β-hydroxysteroid dehydrogenase activity towards those chemicals. Dicofol, organotins and phthalates were among the most effective inhibitors. In contrast, ovarian synthesis of maturation-inducing hormones (20α- and 20β-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 μM, respectively. Triphenyltin, tributyltin and nonylphenol were also inhibitors of estradiol sulfation with IC 50 values of 17, 18 and 41 μM. Overall, the data indicates the interaction of selected chemicals with key enzymatic pathways involved in both synthesis and metabolism of sex hormones. 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Carp testicular microsomes incubated in the presence of androstenedione and different xenobiotics evidenced higher sensitivity of 5α-reductase activity than 17β-hydroxysteroid dehydrogenase activity towards those chemicals. Dicofol, organotins and phthalates were among the most effective inhibitors. In contrast, ovarian synthesis of maturation-inducing hormones (20α- and 20β-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 μM, respectively. Triphenyltin, tributyltin and nonylphenol were also inhibitors of estradiol sulfation with IC 50 values of 17, 18 and 41 μM. Overall, the data indicates the interaction of selected chemicals with key enzymatic pathways involved in both synthesis and metabolism of sex hormones. 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subjects 17β-HSD
20α/β-HSD
5α-Reductase
Androstenedione - pharmacology
Animals
Biological and medical sciences
Carps - metabolism
Endocrine disrupters
Endocrine System - drug effects
Endocrine System - metabolism
Estradiol-SULT
Female
Fish
Fundamental and applied biological sciences. Psychology
Glucuronosyltransferase - metabolism
Liver - enzymology
Male
Microsomes - enzymology
Ovary - drug effects
Ovary - metabolism
Sex Attractants - biosynthesis
Sex Attractants - metabolism
Sulfotransferases - metabolism
Testis - drug effects
Testis - metabolism
UGT
Vertebrates: endocrinology
Xenobiotics - pharmacology
title Effects of endocrine disrupters on sex steroid synthesis and metabolism pathways in fish
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