**4. Modes/mechanisms of actions of EDCs**

**a.** Effect on hormone, nuclear, and nonnuclear receptors: Our understanding of the mecha‐ nisms by which EDCs exert their effect has grown. EDCs were originally thought to exert actions primarily through nuclear hormone receptors [i.e., estrogen receptors (ERs), androgen receptors (ARs), progesterone receptors, thyroid receptors (TRs), and retinoid receptors]. However, recent basic and mechanistic researches show that the underlying mechanisms of their toxicity are much wider than originally envisioned. Thus, other than nuclear receptors, EDCs may also act via nonnuclear steroid hormone receptors (e.g., membrane ERs), nonsteroid receptors (e.g., neurotransmitter receptors such as serotonin receptor, dopamine receptor, and norepinephrine receptor), and orphan receptors [e.g., aryl hydrocarbon receptor (AhR)] [9–11].

