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MitoVasc : physiopathologie cardiovasculaire et mitochondriale


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    Munier and Al

    Munier and Al

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      Separated by coma
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    Le pesticide DDT perturbe l'activité des récepteurs membranaires hormonaux.

    In Vitro Effects of the Endocrine Disruptor p,p'DDT on Human Follitropin Receptor.

    BACKGROUND:

    p,p'DDT is an environmental persistent endocrine disruptor (ED). Several studies have shown an association between p,p'DDT exposure and reproductive abnormalities.

    OBJECTIVES:

    To investigate putative effects of p,p'DDT on the Follitropin receptor (FSHR) function.

    METHODS AND RESULTS:

    We investigated the impact of p,p'DDT on the FSHR activity and its interaction with the receptor, using Chinese Hamster Ovary (CHO) cells stably expressing the human FSHR. p,p'DDT, at 5 µM, increased the maximal response of FSHR to follitropin by 32 ± 7.45%.Otherwise, 5µM p,p'DDT decreased the basal activity and didn't influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin hormone. The potentiating effect of p,p'DDT was specific of FSHR. Moreover, in cells, that didn't express FSHR, the p,p'DDT didn't have effect on cAMP response. So, the potenting effect of p,p'DDT was dependent on FSHR. In addition, p,p'DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist (16a) of FSHR. Basal activity in response to p,p'DDT and potentiation of the FSHR response to FSH by p,p'DDT varied among FSHR mutants with altered transmembrane domains (TMD), consistent with an effect of p,p'DDT via TMD binding. This was corroborated by the results of docking p,p'DDT and 16a into the FSHR transmembrane bundle simultaneously.

    CONCLUSION:

    p,p'DDT acted as a positive allosteric modulator of FSHR in our experimental model. These findings suggest that G Protein-coupled receptors are additional targets of endocrine disruptors.