Membrane Hormone Receptors and Their Signaling Pathways as Targets for Endocrine Disruptors

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.

Advancing Endocrine Disruptors via In Vitro Evaluation: Recognizing the Significance of the Organization for Economic Co-Operation and Development and United States Environmental Protection Agency Guidelines, Embracing New Assessment Methods, and the Urgent Need for a Comprehensive Battery of Tests

“…One of the main difficulties in developing an in vitro assay for endocrine disruption is identifying the relevant endpoints to measure. The endocrine system is involved in a wide range of physiological processes, and there are many different hormones and receptors that can be targeted by endocrine disruptors [ 12 , 13 , 14 , 15 , 16 ]. As a result, it can be difficult to determine which endpoints to measure in an in vitro assay to effectively capture the full range of endocrine disruption effects.…”

Xeno-Estrogenic Pesticides and the Risk of Related Human Cancers

“…Xeno-estrogens are a group of chemicals that disrupt the endocrine system by mimicking the activity of natural estrogens or producing a similar response in the body by other mechanisms. Majorly known persistent organochlorine pesticides (OCPs) and other classes of chemicals present in the environment are known to bind estrogen receptors and produce a physiological response equivalent to the hormone in various organs and tissues [ 2 ]. Therefore, these chemicals can produce adverse effects such as increasing the risk of estrogen-mediated cancers [ 3 ].…”