Endocrine disruptors are chemicals that can alter functions of the endocrine system by several ways. Their risk assessment with regard to REACH legislation remains a challenge. In the present study, we propose an integrative evaluation for the effects of some endocrine disruptors on hormonal balance in male and female adult rats. We focused our work on the last step of steroidogenesis, where two enzymes are implicated: aromatase, which plays a central role by catalyzing the irreversible conversion of androgens to estrogens, and 17β-hydroxysteroid dehydrogenase, which catalyses the conversion of inactive sexual hormones to active ones.
We have evaluated the selected chemicals for their ability to i) modulate the expression and activity of steroidogenic enzymes in gonads, to ii) disrupt hormonal balance, and to iii) disrupt certain fertility parameters, during a sub-acute exposure. Gene expression profile was assessed by RT-qPCR, ex vivo aromatase activity was assessed by the method of tritiated water, blood and gonadal steroid concentrations were evaluated with LCMS/MS.
Our results showed that all treatments induced disturbance of hormonal balance, related or not with gene expression disorders. For example, rats treated with atrazine presented high levels of estradiol and low levels of testosterone. It may be related to aromatase induction observed in testes and ovaries as well as in gonadal primary cultures. A decrease of testosterone level is also observed in male rats treated with methoxychlor, which can be linked not only to aromatase induction, but also to HSD17B3 down-regulation.
These results are part of a work aiming to evidence hormonal concentration modifications related to reproductive toxicology effects in in vitro models compared to in vivo model. Taken together and discussed with regards to extra-gonadal regulation, they contribute to provide information concerning the action of endocrine disruptors, which need to be considered when assessing the effects on human health.