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Endocrine Abstracts (2019) 63 P1000 | DOI: 10.1530/endoabs.63.P1000

ECE2019 Poster Presentations Environment, Society and Governance (15 abstracts)

In vitro effects of the endocrine disruptors DEHP, DBP and BPA on INSL3 receptor (RXFP2)

Valentine Suteau 1, , Louis Gourdin 1, , Claire Briet 1, , Patrice Rodien 1, & Mathilde Munier 1,


1MITOVASC Institute, Angers, France; 2UMR CNRS 6015, INSERM 1083, University of Angers, Angers, France; 3Department of Endocrinology, University Hospital, Angers, France; 4Reference Center for rare Diseases of Thyroid and Hormonal Receptors, Angers, France.


Introduction: Epidemiological and In vivo experimental studies reveal reprotoxic effects of endocrine disruptors (phthalates (DBP, DEHP) and bisphenol A (BPA)). An inverse association was found between the concentration of these endocrine disruptors and the concentration of INSL3. INSL3, a relaxine peptide, is involved in reproductive function, via its cognate receptor, RXFP2. The aim of this study was to characterize the involvement of RXFP2 in the effects of these endocrine disruptors.

Methods: We used HEK293 cells transiently transfected with hRXFP2 to investigate the impact of the endocrine disruptors on RXFP2 activity. Receptor activity was analyzed by measuring intracellular cAMP production.

Results: We first checked that the different PEs tested did not induce cellular toxicity (MTT test). DEHP and DBP at concentrations between 10−10M and 10-4M increased the action of INSL3 by 40%. In the same way, BPA between 10−9 and 10−5M potentiated the response to the hormone by 10 to 25%. This effect was specific to RXFP2 because they did not act on the adenylate cyclase (cAMP synthesis) or on phosphodiesterases (cAMP degradation). The analysis of dose-response curves showed that DEHP, DBP and BPA increased the potency and/or efficacy of INSL3. These compounds also increased the constitutive activity of RXFP2 by about 20%. DEHP, DBP and BPA could act as agonists with positive allosteric modulation.

Conclusion: These findings suggest that RXFP2, as others G protein–coupled receptors, may be involved in the mode of action of DEHP, DBP and BPA in experimental conditions.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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