Biology Reference
In-Depth Information
DHR4 protein. Cycling of
DHR4
transcript in concert with PTTH-
stimulated ecdysone peaks would presumably be a way to help terminate
ecdysone production and regulate the duration of the pulse.
4.2. Termination of ecdysone pulses by feedback regulated
degradation
Although ecdysone production in the PG must be turned off to bring levels
back to basal, circulating ecdysone must also be removed to terminate the
pulse. Two elegant feedbackmechanisms have evolved to rapidly decrease cir-
culating levels of ecdysone following a peak (
Fig. 1.4
). The first mechanism
involves Cyp18a1, a cytochrome P450 enzyme required for the metabolic
inactivation of ecdysone (
Guittard et al., 2011; Rewitz et al., 2010
). Cyp18a1
is required for the rapid decline of the ecdysone titer after the peak that triggers
pupariation. Loss of
Cyp18a1
results in elevated ecdysone levels that disrupt
the mid-prepupal expression of
b
FTZ-F1
, which is necessary for the genetic
response to ecdysone that drives unidirectional progression of development
(
Rewitz et al., 2010
).
Cyp18a1
expression is induced by ecdysone, providing
a mechanism for generating a pulse, where elevated ecdysone levels are
responsible for its eventual decline. In addition to metabolic inactivation,
another mechanism ensures that cellular levels of ecdysone are reduced
following a peak. One of the early ecdysone-inducible genes,
E23
,encodes
an ABC transporter protein (
Hock, Cottrill, Keegan, & Garza, 2000
).
E23
is
one of the last of the early genes to be induced which makes physiological
sense because the function of E23 is to pump ecdysone out of the cells and
reduce cellular concentration. Together with feedback regulation of the
PG activity, these peripheral mechanisms provide an autonomous regulatory
system that determines the duration of the ecdysone pulses.
5. SUMMARY AND PERSPECTIVES
Steroids synthesized in response to signaling pathways including
insulin-like peptides, TGF
b
and other neuropeptides control the develop-
mental transition leading to maturation in worms, insects and mammals.
Recent progress from
Drosophila
research shows that nutrient sensitive insu-
lin signaling and tissue-autonomous size determination are part of the
underlying size-monitoring mechanisms that activate the endocrine system
and initiate maturation once a characteristic size is achieved. An autonomous
genetic size determining program that is dependent on the number of cell
