Biology Reference
In-Depth Information
Romero, & Munck, 2000
) and perhaps decreased anterior pituitary growth
hormone (GH) biosynthesis (
Harvey, Scanes, & Daughaday, 1995
).
Recent findings suggest several molecular mechanisms for the positive
interactions between CS and TH signaling in the acceleration of metamor-
phosis. CSs enhance TH bioactivity, increasing expression of TR and
monodeiodinase genes. They increase maximal nuclear-binding capacity
for T
3
(
Kikuyama et al., 1993; Niki, Yoshizato, & Kikuyama, 1981;
Suzuki & Kikuyama, 1983
), which is paralleled by the upregulation of
tr
mRNAs in
X. laevis
tail and in frog cell lines; this occurs in a synergistic man-
ner with low or subthreshold doses of TH plus CORT causing superinduc-
tion of TRs (
Bonett et al., 2010
). CORT also increased 5
0
-deiodinase
activity and
Dio2
mRNA in tadpoles, thereby increasing T
3
in target tissues
(
Bonett et al., 2010; Darras et al., 2002; Galton, 1990; Kuhn et al., 2005
).
Notably, the action of CORT on
Dio2
was synergistic with T
3
in tadpole
tail (
Bonett et al., 2010
).
Direct TH target genes may also be synergistically regulated by T
3
and
CS through mechanisms that are not directly or immediately dependent on
increased TRs or deiodinases (i.e., direct synergy between TRs and CS re-
ceptors at the target gene). For example, Kr¨ppel-like factor 9 (
Klf9
; also
known as
BTEB1
), a direct T
3
target gene, is induced by CORT
(
Bonett, Hu, Bagamasbad, & Denver, 2009
) and is superinduced in tadpole
tissues with rapid kinetics by combined treatment with T
3
plus CORT
(P. Bagamasbad, R.M. Bonett, and R.J. Denver, unpublished data). Other
genes are synergistically regulated by TH and CS, which could explain the
mechanism by which these two hormones cooperate to accelerate metamor-
phosis (
Kulkarni et al., 2012
).
2. NEUROENDOCRINE CONTROL OF METAMORPHOSIS
The vertebrate neuroendocrine system is comprised of the hypothal-
amus and the pituitary gland (
Fig. 7.1
). The importance of hypothalamic
control of metamorphosis has long been recognized (
Denver, 1996;
Kikuyama et al., 1993
). The pituitary hormones that control TH and CS
production, TSH and adrenocorticotropic hormone (ACTH), respectively,
are primarily under stimulatory hypothalamic control in amphibians
(
Denver, 1996
). The neuroendocrine system serves as an interface between
the central nervous system and the endocrine system, and transduces signals
derived from the external and internal environments into appropriate phys-
iological/developmental responses.
