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In mammals (De Vito et al. 1999; Ahmed et al. 2008), amphibians (Fort et al. 2007), and
teleosts (Brown et al. 2004; Blanton and Specker 2007), T4 is the main product released by
thyroid follicles into the circulation. It is then bound to TH-binding proteins (transport
proteins) and carried to target tissues. In peripheral tissues, T4 is converted into triiodothy-
ronine [3,5,3-triiodo-l-thyronine (T3)] by action of a complex of deiodinase enzymes that
removes one of the two outer ring iodines (Blanton and Specker 2007; Fort et al. 2007; Eales
2006; Zoeller et al. 2007). T3 has higher affinity than T4 to the thyroid receptors (TRα or
TRβ); it is the most active hormone and is responsible for most biological effects. Thyroxin
and T3 are rendered inactive by the loss of an inner ring iodine catalyzed by another
group of deiodinase enzymes and eliminated by biliary excretion. The thyroid condition
is usually evaluated by measuring T4 and T3; moreover, it is these two hormones that are
generally associated with the term “thyroid hormone.” THs are evolutionarily conserved
molecules present in all extant vertebrates and some invertebrates (Heyland et al. 2005).
The action mechanisms of THs through nuclear receptors that influence gene expression
is also strongly conserved across the vertebrate taxa (Whitfield et al. 1999; Bertrand et al.
2004; Buchholz et al. 2006). In addition, because of this highly conserved nature of TH
chemistry, synthesis, signaling, and regulation, environmental factors that affect thyroid
function or TH signaling in one species may well affect thyroid function or TH signaling
in others including humans (Miller et al. 2009).
Molecular signaling pathways regulated by THs affect development, energy balance,
and metabolism for all taxonomic groups of vertebrates. It is understood that THs regu-
late, at least in part, the classical larva-to-juvenile metamorphosis of teleosts and amphib-
ians (Paris et al. 2008a) and the embryo-to-larva transformation of teleosts (Liu et al.
2002). Concerning amphibian metamorphosis, many of the morphological changes are
TH-dependent, among them the resorption of the tail, development of limbs, and restruc-
turing of the head (Shi 2000; Buchholz et al. 2005; Carr and Norris 2006). Among teleosts,
THs are essential for early development, particularly for larval-juvenile transitions and
induction of metamorphosis (craniofacial rearrangement and loss of bilateral symmetry)
in flatfish (Yamano et al. 1994; Inui et al. 1995; Power et al. 2001; Yamano 2005; Schreiber et
al. 2006; Shiao and Wang 2006; Blanton and Specker 2007; Klaren et al. 2008). Many studies
have correlated the necessity of THs for gonadal development and reproduction in most
teleosts (Weber et al. 1992; Cyr and Eales 1996; Van der Ven et al. 2006; Mukhi and Patiño
2007). In mammals (Zoeller and Rovet 2004), THs are also essential for development. The
crucial role of THs in brain development for mammalian and nonmammalian species has
been further described (Ahmed et al. 2008; Koibuchi 2008; Leonard 2008; Ahmed et al.
2010; Sigrun and Heike 2010).
Given the fundamental role of TH for physiologic function and normal development in
all vertebrates and some invertebrates, the identification of environmental factors that may
adversely affect thyroid function and/or TH signaling is very important as is an evalua-
tion of their ability to adversely affect ecosystems. Main endpoints used for the assess-
ment of HPT disruption in most mammals, teleosts, and amphibians are as follows: central
effects-thyroid histopathology; plasma binding proteins and plasma TH levels; TH deio-
dination and metabolism; target tissue and receptor level endpoints; whole animal end-
points (Brucker-Davis 1998; Pearce and Braverman 2009; Carr and Patiño 2010).
Some EDCs have a structure relatively similar to that of thyroxin (T4) and triiodothy-
ronine (T3). Thus, these compounds are mainly characterized by their ability to have
direct actions on TH receptors, inhibit thyroidal iodine uptake, inhibit TH synthesis (thy-
roperoxidase activity), alter deiodinase functions in peripheral tissues, decrease T4 half-
life by activating hepatic enzymes, and displace TH from TH-binding proteins (transport
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