Interference with Systemic Negative Feedback Regulation as a Potential Mechanism for Nonmonotonic Dose-Responses of Endocrine-Disrupting Chemicals.

ABSTRACT:

Background

Endocrine-disrupting chemicals (EDCs) often exhibit nonmonotonic dose-response (NMDR) relationships, posing significant challenges to health risk assessment and regulations. Several molecular mechanisms operating locally in cells have been proposed, including opposing actions via different receptors, mixed-ligand heterodimer formation, and receptor downregulation. Systemic negative feedback regulation of hormone homeostasis, which is a common feature of many endocrine systems, has also been invoked as a mechanism; however, whether and how exactly such global feedback structure may underpin NMDRs is poorly understood.

Objectives

We hypothesize that an EDC may compete with the endogenous hormone for receptors (i) at the central site to interfere with the feedback re

SUBMITTER: Shi Z 

PROVIDER: S-EPMC11398479 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature