title: Potency matters: thresholds govern endocrine activity.
abstract: Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential. This obligatory ability to discriminate important hormonal signals from background noise can be used to define thresholds for induction of hormonal effects, without which normal physiological functions would be impossible. From such thresholds, safe levels of exposure can be estimated. This brief review highlights how the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning.
authors.affiliation: Applied Pharmacology & Toxicology, Inc., C.E.H.T, University of Florida, Department of Physiological Sciences, 2250 NW 24th Ave., Gainesville, Fl 32605, United States. Electronic address: cjborgert@apt-pharmatox.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Borgert
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Baker
authors.forename: John C
authors.initials: JC
authors.lastname: Matthews
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000009:adverse effects* / Q000494:pharmacology*; D004703:Endocrine System / Q000187:drug effects*; D005062:European Union; D006728:Hormones / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans
chemical_list: D052244:Endocrine Disruptors; D006728:Hormones
keywords: Endocrine active substances; Endocrine disruption; Endocrine pharmacology; Hormone affinity; Hormone efficacy; Hormone potency; Potency threshold