Thyroid-like hormone signaling in invertebrates and its potential role in initial screening of thyroid hormone systemdisrupting chemicals

摘要

This review examines the presence and evolution of thyroid-like systems in selected aquatic invertebrates to determine thepotential use of these organisms in screens for vertebrate thyroid hormone axis disrupting chemicals (THADCs). Such ascreen might support the phasing out of some vertebrate testing. Although arthropods including crustaceans do not containa 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 toinduce the nuclear thyroid hormone receptor (THR). Thyroid hormone may act in these phyla through interaction with amembrane integrin receptor. Thyroid hormone regulates inter alia metamorphosis but, unlike in vertebrates, this does notoccur via receptor activation by the ligands triiodothyronine (T3) and thyroxine (T4). Instead, the unliganded nuclear receptoritself 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 screenthat is sensitive to vertebrate THADCs that interfere with thyroid hormone synthesis or metabolism along with interactionwith membrane receptors. The review makes some recommendations for the need to develop an appropriate test method.