Biology Reference
In-Depth Information
Liang, Sedgwick, & Shi, 1997; Shi & Brown, 1993
). Only the amino acid
permeases have so far received attention with regard to their function during
tadpole metamorphosis. The T
3
-inducible gene
iu12
from
Xenopus laevis
in-
testine (
Liang et al., 1997; Shi & Brown, 1993
) encodes a subunit of a
heterodimeric amino acid permease complex (System L;
Ritchie et al.,
2003; Torrents et al., 1998
). This permease complex efficiently transports
T
3
and T
4
when expressed in the
Xenopus
oocyte expression system but is
inhibited by reverse T
3
(
Ritchie et al., 1999
). Overexpression of System
Lin
Xenopus
oocytes increased cytoplasmic and nuclear delivery of THs
from the external medium and enhanced transcriptional activation by
TRs (
Ritchie, Hayashi, Shi, & Taylor, 2002
). By contrast, blocking endog-
enous System L activity in mammalian cells reduced both TH uptake and
TR function (
Ritchie et al., 2003
). The fact that
iu12
is a T
3
-inducible gene
suggests that it could play a role in mediating T
3
uptake by cells during tad-
pole metamorphosis (
Liang et al., 1997
).
Upon entering cells, THs may bind to a series of intracellular-binding
proteins, termed cytoplasmic TH-binding proteins (CTHBPs) that repre-
sent several classes of multifunctional proteins. These proteins may have a
variety of enzymatic activities; for example, three genes isolated from
X. laevis
code for (1) a cytosolic aldehyde dehydrogenase which catalyzes
the formation of retinoic acid (
Yamauchi & Tata, 1994
), (2) an M2 pyruvate
kinase (
Shi, Liang, Parkison, &Cheng, 1994
), and (3) protein disulfide isom-
erase (PDI; induced by T
3
in tadpole brain;
Denver et al., 1997
), which cat-
alyzes disulfide bond formation and human PDI has been shown to bind TH
with high affinity (
Cheng et al., 1987; Yamauchi et al., 1987
). These
CTHBPs may transport THs within the cytoplasm to the nucleus to bind
to TRs, or alternatively, they may serve as chelators to limit the cellular free
TH concentration (
Shi, 2000
). It is also possible that TH may regulate the
enzymatic activity of these proteins (
Ashizawa & Cheng, 1992
).
1.2. Corticosteroids
1.2.1 CS production during metamorphosis
In addition to TH, CSs, the primary vertebrate stress hormones, play impor-
tant roles in amphibian metamorphosis. Like TH, the production of CS
changes with development and likely reflects the functional maturation of
the hypothalamo-hypophyseal-interrenal axis. The major CS produced
by the amphibian interrenal glands are corticosterone (CORT) and aldoste-
rone (ALDO) (
Carstensen, Burgers, & Li, 1961; Macchi & Phillips, 1966
).
