Thyroid‐like hormone signaling in invertebrates and its potential role in initial screening of thyroid hormone system disrupting chemicals

This review examines the presence and evolution of thyroid‐like systems in selected aquatic invertebrates to determine the potential use of these organisms in screens for vertebrate thyroid hormone axis disrupting chemicals (THADCs). Such a screen might support the phasing out of some vertebrate testing. Although arthropods including crustaceans do not contain a functional thyroid signaling system, elements of such a system exist in the aquatic phyla mollusks, echinoderms, tunicates, and cephalochordates. These phyla can synthesize thyroid hormone, which has been demonstrated in some groups to induce the nuclear thyroid hormone receptor (THR). Thyroid hormone may act in these phyla through interaction with a membrane integrin receptor. Thyroid hormone regulates inter alia metamorphosis but, unlike in vertebrates, this does not occur via receptor activation by the ligands triiodothyronine (T3) and thyroxine (T4). Instead, the unliganded nuclear receptor itself controls metamorphosis in mollusks, echinoderms, and tunicates, whereas the T3 derivative tri‐iodothyroacetic acid (TRIAC) acts as a THR ligand in cephalochordates. In view of this, it may be possible to develop an invertebrate‐based screen that is sensitive to vertebrate THADCs that interfere with thyroid hormone synthesis or metabolism along with interaction with membrane receptors. The review makes some recommendations for the need to develop an appropriate test method. Integr Environ Assess Manag 2023;19:63–82. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). KEY POINTS This article examines thyroid‐like hormone systems in invertebrates and finds that they exist in several groups, including mollusks, echinoderms, tunicates, and cephalochordates. It is concluded that some invertebrate groups may provide a suitable basis for the development of screening tests for certain chemicals that disrupt the thyroid systems of vertebrates. It is likely that invertebrate‐based tests for vertebrate thyroid disrupters will be able to detect those that interfere with thyroid hormone synthesis and metabolism, but not those that act agonistically or antagonistically at the thyroid receptor. The development of invertebrate‐based tests for vertebrate thyroid disrupters would likely reduce the need for some vertebrate screening tests, which would be desirable from an ethical point of view.