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development are highly conserved between teleosts and mammals (
Alt
et al., 2006; Porazzi, Calebiro, Benato, Tiso, & Persani, 2009
), as are
the deiodinases that regulate TH activity (
Itoh et al., 2010; Orozco &
Valverde-R, 2005; Power et al., 2008
). In response to pituitary thyrotro-
pin (TSH), thyroid follicles produce TH in the form of thyroxine (T4).
Circulating plasma levels of T4 increase markedly at the onset of metamor-
phosis in several teleost species (
Fig. 5.7
), suggesting that the thyroid is
highly active during this period. This is further consistent with the results
of radioiodide uptake assays (
Brown, 1997
;D.M.Parichy,unpublished)
and enzyme-linked immunoassays performed in zebrafish (
Chang et al.,
2012
). T4 is converted in peripheral tissues by deiodinase enzymes
(DIO1 and DIO2) into the genomically active form, tri-iodothyronine
(T3). Both T3 and T4 are inactivated by a third deiodinase, DIO3. Thus,
the expression and activity of deiodinases regulate TH bioactivity and
availability. In teleosts, these genes are expressed in spatially and temporally
specific manners during postembryonic development, with
dio1
and
dio2
increasing in expression immediately before and during metamorphic
climax of several species (
Campinho et al., 2010; Itoh et al., 2010
).
T3 serves as the ligand for nuclear TH receptors (TRs), which typically
activate expression of target genes in the presence of the hormone, and
repress expression in its absence. All teleosts examined possess at least two
isoforms of THRs: TR
a
and TR
b
, and many posses additional copies of
these loci, possibly owing to an ancient, teleost-specific genome duplication
(
Hoegg, Brinkmann, Taylor, &Meyer, 2004; Ravi & Venkatesh, 2008
); for
example, zebrafish exhibit two TR
a
loci,
thraa
and
thrab
, though only a
single TR
b
locus,
thrb
. In species that have been examined so far, TRs
increase in expression prior to and during metamorphic climax (
Fig. 5.8
).
Thus, TR-mediated TH signaling appears to play a critical role in the
metamorphosis of teleosts examined. Nevertheless, although TH is by far
the best-studied hormonal factor in teleosts, TSH and TH titers and expres-
sion of DIOs and TRs remain undocumented for the vast majority of teleost
families. Thus, the requirement or sufficiency for TH in metamorphosis re-
mains unknown in most fish; moreover, the genetic targets and molecular
mechanisms of hormonal action remain largely unclear.
3.2. Non-TH mediators of metamorphosis
In addition to TH, other endocrine factors contribute to metamorphosis as
well. GH activates insulin-like growth factor (IGF) pathways, stimulating
cellular proliferation and increasing basal metabolic rate. Spikes in plasma
