Biology Reference
In-Depth Information
fibroblasts, is undetectable before late prometamorphosis at which time
expression increases markedly and is maintained through the end of metamor-
phosis (
Cai & Brown, 2004
). This late expression of
Dio2
is hypothesized to
generate bioactive T
3
at an appropriate developmental stage to accelerate tail
resorption. Neither
Dio2
nor
Dio3
mRNAs are expressed in tail muscle cells
(
Berry et al., 1998; Bonett, Hoopfer, & Denver, 2010
); nonmuscle tail cells
mayinactivateT
4
during pre- and prometamorphosis to protect tail muscle
cells from apoptosis, and subsequently generate high local concentrations of
T
3
to promote tail muscle cell apoptosis at metamorphic climax.
Tissue transformations during metamorphosis are asynchronous: some
tissues respond early to low plasma concentrations of TH (e.g., hindlimb,
brain), while other tissues respond later in development and require high
TH concentration (e.g., intestine, tail—discussed above). The expression
patterns of the monodiodinase genes may play a key role in establishing tissue
competence to respond to the TH signal. For example, for tissues that
respond early in metamorphosis to TH like the retina and hindlimb,
Dio2
expression was high during early prometamorphosis but declined at
metamorphic climax. The importance of 5
0
-deiodinase activity for hindlimb
development is supported by findings that T
4
has no effect on the hindlimb
release of glucocorticoids which are transported in the blood bound to corticosteroid-
binding globulin. Cellular uptake of T
3
and T
4
is achieved by organic anion,
monocarboxylate, and amino acid transporters; there is also evidence that thyroid hor-
monesmay enter cells bound to transthyretin via a receptor-mediatedprocess. Glucocor-
ticoids enter cells by passive diffusion across the plasma membrane. Upon entering the
cell, thyroid hormone is bound by cytosolic-binding proteins, some of which (the
monodeiodinases) convert the hormone to either active (T
3
; deiodinases types I and II)
or inactive forms (reverse T
3
[rT
3
], diiodothyronine [T
2
]; deiodinase type III). TRs form
heterodimers with RXRs and are bound to DNA in the unliganded form where they
actively repress gene transcription. Upon thyroid hormone binding to TR, gene transcrip-
tion is derepressed and activated. Upon entering the cell, glucocorticoids bind to corti-
costeroid receptors (glucocorticoid receptor [GR] or mineralocorticoid receptor [MR])
that are located in the cytosol bound to heat shock proteins (the
). Hormone
binding causes a conformational change in the receptor, the release of heat shock pro-
teins, and dimerization and translocation of receptors to the nucleus where they bind
DNA to activate or repress target genes. When cells are exposed to low concentrations
of thyroid hormone plus glucocorticoids, genes such as the TRs, deiodinase type 2,
and the thyroid hormone-inducible transcription factor Klf9 are activated in a synergistic
manner. This leads to enhanced sensitivity of cells to the actions of thyroid hormone,
which acceleratesmetamorphosis. “þ” indicates an increase and “” indicates a decrease
in the regulated variable.
“
foldosome
”
