Biology Reference
In-Depth Information
Peripherally, the availability and activity of TH is precisely regulated
within cells. In mammals, TH is transported into target cells via TH trans-
porters, which actively and preferentially import the hormone across the
plasma membrane (
Hennemann et al., 2001
). TH transporters have been
studied in
X. laevis
(
Connors, Korte, Anderson, & Degitz, 2010; Ritchie
et al., 2003
), but there have been no studies using salamanders. Deiodinases
have received considerable attention because they directly activate or inac-
tivate intracellular forms of TH in amphibians (
Buscaglia et al., 1985;
Galton, 1991; Kuhn et al., 2005
). The low activity T4 form of TH that is
delivered to cells is converted intracellularly by deiodinase-type 2 (DIO2)
into highly active 3,5,3
0
-triiodothyronine (T3). A second deiodinase,
DIO3, inactivates intracellular T3. Although T4 may participate in cellular
signaling (
Caria, Dratman, Kow, Mameli, & Pavlides, 2008
), T3 is the pri-
mary TH signaling molecule in anurans (
Denver et al., 2002
) and presum-
ably this is also true for salamanders, acting through nuclear receptors (
thra
,
thrb
) that function as transcription factors. The higher activity of T3 is asso-
ciated with a higher affinity for TH receptor (TR) binding. The binding of
T3 activates transcriptional regulatory networks in cell-specific manners
(
Shi, 2000
). TH is also known to cause cellular changes via nongenomic
mechanisms, including membrane receptors, transporter molecules, and cyto-
plasmic receptors that elicit changes in cells through signaling pathways (
Caria
et al., 2008; Cheng, Leonard, & Davis, 2010; Davis, Leonard, & Davis, 2008;
Furuya, Lu, Guigon, & Cheng, 2009
). The effects of these nongenomic
mechanisms of TH action and their role in amphibian metamorphosis have
yet to be studied in detail, however,
Buchholz, Tomita, Fu, Paul, and Shi
(2004)
used transgenic analysis to show that TR is sufficient to mediate
TH signaling during metamorphosis in
X. laevis
. Regulation of deiodinases,
T4/T3 concentrations, and developmental expression of TRs help explain
how a single hormone can coordinate responses among different cell types,
and more generally regulate the temporal sequence of remodeling events
during amphibian metamorphosis (
Brown & Cai, 2007
).
4. HORMONAL BASIS OF PAEDOMORPHOSIS
Only a year after,
Gudernatsch (1912)
established TH as the anuran
metamorphic hormone, TH was shown by Laufberger to induce metamor-
phosis in
A. mexicanum
(Mexican axolotl) (reviewed by
Huxley & Hogben,
1922
). Over the next few decades, the responsiveness of many different
paedomorphic salamanders to TH was investigated. Studies showed that
