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Membrane Hormone Receptors and Their Signaling Pathways as Targets for Endocrine Disruptors
Yves Combarnous1, Thi Mong Diep Nguyen1,2
1INRAe, CNRS, Tours University Joint Unit, Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France.
Abstract:
The endocrine disruptors are mostly small organic molecules developed for numerous and very diverse industrial applications. They essentially act through nuclear receptors with small and hydrophobic endogenous ligands. Nevertheless, potential adverse effects through membrane hormone receptors cannot be ruled out, and have indeed been observed. The present paper reviews how orthosteric and allosteric binding sites of the different families of membrane receptors can be targets for man-made hydrophobic molecules (components of plastics, paints, flame retardants, herbicides, pesticides, etc.). We also review potential target proteins for such small hydrophobic molecules downstream of membrane receptors at the level of their intracellular signaling pathways. From the currently available information, although endocrine disruptors primarily affect nuclear receptors' signaling, membrane receptors for hormones, cytokines, neuro-mediators, and growth factors can be affected as well and deserve attention.
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