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lumbar spinal cord of male rats, there are two motor
nuclei that innervate striated muscle of the penis: the
spinal nucleus of the bulbocavernosus (SNB) and the
dorsolateral nucleus. As one might expect, these nuclei
and the muscles that they innervate are present in
males but are nearly absent in female rats. This sexual
dimorphism arises from the selective loss of motor
neurons in female rats. During the first 10 postnatal
days, the total number of SNB neurons decrease
by nearly 70% in females, although the number only
decreases by about 30% in males (Figure 7.20).
However, when females are treated with the androgen
steroid hormone, testosterone, the amount of cell death
is decreased and resembles the pattern seen in males
(Nordeen et al., 1985). When males are castrated and
reared with an androgen antagonist, flutamide, their
SNB neurons are as scarce as in female rats (Breedlove
and Arnold, 1983). The endogenous androgen signal
probably keeps more male SNB neurons alive by
keeping the target muscles alive and preserving target-
derived survival factors. In fact, when females are
treated with androgen, but also receive a treatment
that blocks signaling at either TrkB, TrkC, or the
CNTFR, there is very little sparing of SNB motor
neuron number (Freeman et al., 1997, Xu et al., 2001).
Endocrine signals can lead to extensive remodeling
throughout the nervous system. In the moth, a great
many neurons are necessary in larvae, or are required
for the process of metamorphosis from caterpillar to
pupa to moth. A surge of the steroid hormone, 20-
hydroxecdysone (20E), triggers each molt, during
which the larva sheds its cuticle and grows. The 20E
also acts as a trigger for normal cell death. The small
pulse of 20E that triggers the formation of a pupa,
also acts directly on a specific set of abdominal motor
neurons to bring about their death. These motor
neurons are not dependent on their target for survival,
in contrast to those in vertebrates. Instead, these motor
neurons can be placed in culture, and killed by expo-
sure to 20E at a specific time in their development
(Hoffman and Weeks, 1998). The final prolonged ele-
vation of 20E causes the adult moth to emerge from its
pupa. As the level of 20E falls, there is a second wave
of cell death during which nearly 40% of abdominal
neurons are lost (Truman and Schwartz, 1984; Zee and
Weeks, 2001). In fruit flies, there are about 300 neurons
in the ventral cord that express much higher levels of
the 20-HE receptor (EcR), and these are precisely the
cells that die at metamorphosis (Robinow et al., 1993).
Apparently, the cells that are to be eliminated become
extremely dependent on 20E. This period of cell death
can be delayed by treatment with 20E in both the moth
and fruit fly. The molecular signals that mediate
ecdysone-induced cell death are quite similar to those
found in other systems (Hoffman and Weeks, 2001;
Buszczak and Segraves, 2000).
Endocrine signaling is also responsible for neuron
death during vertebrate metamorphosis (Decker, 1976;
1977). The surge of thyroxine that initiates metamor-
phosis from tadpole to frog causes lysosomal activity
to increase in motor neurons. The motor neurons that
innervate regressing tail musculature of tadpoles are
eliminated directly by a thyroid hormone signal. Thy-
roxine exposure has also been shown to elicit cell death
in a region of the adult zebra finch forebrain that is
Control female
Control male
base of
Castration &
FIGURE 7.20 Hormonal influence on SNB motor neuron sur-
vival. A. Areas of the lumbar spinal cord that innervate perineal
muscles in male rats are nearly absent in female rats, owing to motor
neuron death during development. B. Male rats exhibit a greater
number of SNB motor neurons. C. When neontal female rats are
treated with the androgen steroid hormone, testosterone, SNB motor
neuron death is decreased. D. In contrast, when neontaal males are
castrated and reared with an androgen antagonist, flutamide, SNB
motor neurons display increased cell death. The target muscle size
is affected by each treatment and appears to explain the effect of
hormone. (Adapted from Nordeen et al., 1985; Breedlove and
Arnold, 1983)
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