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2009a; Kikuyama et al., 1993
). As in other vertebrates, T
3
has greater
biological activity than T
4
in amphibia owing to the TH receptors
(TRs) having 10-15 times greater affinity for T
3
than for T
4
(
Frieden,
1981; Leonard & Visser, 1986; Lindsay, Buettner, Wimberly, & Pittman,
1967; Oppenheimer, Schwartz, & Strait, 1995; Rosenkilde, 1978;
Wahlborg, Bright, & Frieden, 1964; White & Nicoll, 1981
).
1.1.1 TH metabolism
An important point of control of TH bioactivity is at the target tissues, where
monodeiodinase enzymes convert T
4
to T
3
,orinactivateT
4
and T
3
(
Fig. 7.1
).
The monodeiodinases catalyze two basic reactions: a 5
0
-monodeiodination
(outer ring) that results in bioactivation; and a 5-monodeiodination (inner
ring) that results in bioinactivation of the substrate, T
4
or T
3
.Therearethree
types of vertebrate deiodinases (types I, II, and III) that differ in their substrate
specificity, kinetics, and sensitivity to inhibitors. Type I catalyzes both 5- and
5
0
-, type II 5
0
-, and type III 5-deiodination (
St Germain, Galton, &
Hernandez, 2009
). Type II and type III, but not type I enzyme activities have
been detected in tadpole tissues, and although frogs have a type I (
Dio1
)gene,
little is known about its expression or function (
Becker, Stephens, Davey,
Schneider, & Galton, 1997; Dubois et al., 2006; Kuiper et al., 2006
).
Three deiodinase genes have been isolated in amphibian species (
Brown,
2005
). The
Dio2
(type II) and
Dio3
(type III) genes exhibit tissue-specific
and developmental stage-specific expression patterns (
Becker et al., 1997;
Brown, 2005; Cai & Brown, 2004
). The expression patterns correlate with
the asynchronous tissue morphogenesis, and the roles that the deiodinases
play in modulating intracellular T
3
concentration during metamorphosis
(
Brown, 2005; St Germain et al., 2009
). In many cells, both enzymes
may be expressed, and the relative expression levels may establish a type
of push-pull mechanism that regulates intracellular T
3
concentration
(
St Germain et al., 2009
). Alternatively, in some tissues, the two genes show
different temporal dynamics, leading to hormone inactivation or activation
at different developmental stages.
For example,
Dio3
mRNA is expressed in several cell types in tadpole tail,
but not in tail muscle cells (
Berry, Schwartzman, & Brown, 1998
); both
Dio3
mRNA and 5-deiodinase activity increase during late prometamorphosis (NF
stage 59-61) but then decline sharply at metamorphic climax (
Brown et al.,
1996; St Germain et al., 1994
). This pattern of
Dio3
expression may protect
the tadpole tail, an essential locomotory organ, from premature resorption
(
Brown, 2005
). By contrast,
Dio2
expression, which occurs mainly in tail
