Les effets du clotrimazole sur la stéroïdogenèse testiculaire chez le poisson zèbre

Abstract : Clotrimazole (CLO) is a pharmaceutical fungicide that has been recently detected in aquatic environment but little is known about its endocrine disrupting potency in fish. In vivo exposures of male zebrafish to CLO led to inductions of steroidogenic gene and protein expressions. Using zebrafish testicular explant culture, no effect of CLO was observed on transcript levels of steroidogenic enzymes but it inhibited 11 ketotestorone (11-KT) release in the medium. It suggests that CLO does not act directly on testis. Induction of these genes could be interpreted as a compensatory biological response to inhibition of cytochrome P-450 dependent steroidogenic enzymes. To support this hypothesis, a network of functional genes of the pituitary-gonad axis was used. We showed that CLO induce a cascade of molecular events in pituitary and testes. Transcript levels of genes encoding for folliculo- stimulating hormone (FSH), testicular FSH receptor and steroidogenic enzymes were induced. These molecular events are consistent with the involvement of FSH in inducing steroidogenic gene expressions to compensate the inhibitory action of CLO on 11-KT synthesis. Our study highlights the relevance of studying a network of genes of the pituitary-gonad axis to investigate the mode of action of compounds acting as inhibitor of P450-steroidogenic enzymes.
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Damien Baudiffier, François Brion, Nathalie Hinfray, Jean-Marc Porcher. Les effets du clotrimazole sur la stéroïdogenèse testiculaire chez le poisson zèbre. Rapport Scientifique INERIS, 2012, 2011-2012, pp.36-38. ⟨ineris-01869419⟩

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