Biology Reference
In-Depth Information
during amphibians and teleost fishes postembryonic development because of
their role in controlling metamorphosis, much less is known in other ver-
tebrates. Indeed in mammals, THs are mostly studied for their endocrine
role in adult, especially for medical purposes such as heart rate control, ther-
mogenesis, or regulation of metabolism. Here, we focus mainly on amni-
otes, the group of vertebrates clustering mammals and sauropsids (birds,
crocodiles, turtles, lizard, and snakes), in order to provide a general view
on the role played by TH in the postembryonic development of these taxa.
This is needed in order to compare on firm ground how metamorphosing
and nonmetamorphosing vertebrates use TH for controlling their post-
embryonic development.
2. TH SIGNALING: THE BASICS
THs are quite unusual signaling molecules, as they are iodinated: the
hormone is formed by the condensation of two aromatic rings of tyrosine
residues coupled with iodine atoms. The cycle linked to the amino acid rad-
ical is called the inner ring and the other one, the outer ring. Each cycle can
carry two iodine atoms in positions 3 and 5 (
Hulbert, 2000
). Two forms of
the hormone are considered as biologically relevant: the thyroxine or
3,5,3
0
,5
0
tetraiodothyronine also known as T4 that carries four iodine atoms
and the 3,3
0
,5 triiodothyronine or T3 that is deiodinated at position 5
0
.
In most species, the thyroid gland mainly produces T4, which is trans-
formed into T3 in peripheral organs by the action of outer-ring deiodinase
(
Fig. 14.1
). T4 and T3 do not have the same affinity for the TRs; indeed, T3
has a 10-fold higher affinity than T4 and is thus considered as the biologically
active compound (
Hulbert, 2000
). However, it is possible that T4 plays a
specific role in some organs in which outer-ring deiodinases are not active.
Similarly, several data suggest that a T3 metabolite 3,5 diiodothyronine or
3,5-T2 may be an active compound in specific conditions (
Ball, Sokolov, &
Chin, 1997
). It is becoming increasingly clear that deiodination, that is the
removal of an iodine atom in the outer or inner ring, is an important control
mechanism of the TH activity. Deiodination is performed by three
paralogous enzymes in vertebrates, D1, D2, and D3 deiodinases, that are
selenoproteins (
Bianco & Kim, 2006
). The outer-ring deiodination trans-
forms the native form T4 into the active form T3 and is performed by
D1 and D2. It is thus an activating deiodination. By acting on T3, it can
produce 3,5-T2, as mentioned previously (
Ball et al., 1997
). The inner-ring
deiodinase transforms T4 into the inactive reverse T3 (rT3; 3,3
0
,5
0
