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Functional profiling of bisphenols for nuclear receptors
Marina Grimaldi1, Abdelhay Boulahtouf1, Lucia Toporova1
1Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, ICM, Univ. Montpellier, 34090, Montpellier, France.
Toxicology
|April 6, 2019
Summary
This study evaluated 24 bisphenols for their effects on nuclear receptors. Many bisphenols showed hormonal activity, highlighting the need for safer alternatives to Bisphenol-A (BPA).
Area of Science:
- Endocrinology
- Toxicology
- Molecular Biology
Background:
- Bisphenol-A (BPA) is a widely produced chemical linked to various health issues, including reproductive and developmental problems, metabolic disruption, and hormone-dependent cancers.
- BPA and its analogs are known to interact with key nuclear receptors (NRs), including estrogen receptors (ERs), estrogen-related receptor gamma (ERRγ), pregnane X receptor (PXR), androgen receptor (AR), and progesterone receptor (PR).
- The widespread use of BPA necessitates the development of safer alternatives with reduced endocrine-disrupting potential.
Purpose of the Study:
- To investigate the impact of 24 different bisphenols on the activity of selected nuclear receptors (NRs).
- To compare the nuclear receptor modulation profiles of various bisphenols against known targets of BPA.
- To provide data-driven guidance for designing safer bisphenol substitutes with diminished hormonal activity.
Main Methods:
- Utilized reporter cell lines engineered to detect the activation or inhibition of specific nuclear receptors.
- Screened a panel of 24 bisphenol compounds for their effects on ERα, ERβ, ERRγ, PXR, AR, PR, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR).
- Quantified the differential modulation of nuclear receptor activity induced by each bisphenol.
Main Results:
- Bisphenols exhibited diverse effects on nuclear receptor activity, with no single compound mimicking BPA's full profile.
- Estrogen receptors (ERs), ERRγ, and PXR were generally activated by most tested bisphenols.
- Several bisphenols functioned as antagonists for AR, PR, GR, and MR, while compounds like BPA, BPC, and BPE modulated multiple NRs.
Conclusions:
- The study demonstrates that bisphenols possess varied and distinct interactions with nuclear receptors.
- The findings underscore the complexity of bisphenol endocrine activity and the potential for off-target effects.
- These results offer crucial insights for the rational design of bisphenol alternatives with reduced endocrine-disrupting properties.
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