Modélisation de la perturbation de la synthèse des hormones ovariennes par les produits chimiques chez les mammifères

Abstract : A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. We know by now that some environmental contaminants may have endocrine disrupting effects. Interfering with steroidogenic enzymes, for example, may influence steroid secretion and thus lead to reproductive toxicity. Yet, predictions of such toxic effects on the basis of in vitro data are a challenge, because the complexity of the endocrine system is not yet captured by in vitro assay systems. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model was shown to correctly predict ovarian estradiol concentrations after exposure of female rats to atrazine and letrozole.
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Frédéric Y. Bois. Modélisation de la perturbation de la synthèse des hormones ovariennes par les produits chimiques chez les mammifères. Rapport Scientifique INERIS, 2013, 2012-2013, pp.32-33. ⟨ineris-01869456⟩

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