Front Matter

(Rick Simeone) #1
Why Testosterone is Essential for Engineering a Male Brain 205

prenatally. They also cultured the primary oSDN in vitro and showed that
testosterone stimulates morphological differentiation of cultured fetal lamb
neurons derived from the cerebral cortex and hypothalamus by increasing
neurite outgrowth and size. These data suggest that testosterone acts as a
morphogenic signal for developing sheep neurons and by so doing contributes
to the maturation of a fully masculine brain. The result establishes that sexual
differentiation during a long gestation (as in humans) occurs prior to birth.
Another important study, carried out by Zuloaga et al. [115], showed that
exposure to testosterone early in fetal life imparts a monumental effect on vari­
ous parts of the brain that are designed to engineer key features of the male
brain. The study demonstrated that the effects of testosterone are mediated
primarily by binding of testosterone (androgen) to its specific receptors (ARs).
ARs found on various parts of the developing fetal brain become relatively
larger and have more neuron and neuronal connects in males compared with
female counterparts in all mammalian species.
Of course, it is established that in the male brain, activation of AR normally
mediates masculinization of the nervous system and behavior. Some of the first
evidence for this idea came from an analysis of motoneurons in the spinal
nucleus of the bulbocavernosus (SNB; Figure  7.12), which mediates penile
reflexes during intercourse. There is a sex difference in the number of SNB
motoneurons that are dependent on AR activation, with males having greater
numbers than females.
Morphology of the posterodorsal medial amygdala (MePD; Figure  7.12),
which receives olfactory and pheromonal information and is important for
certain male sexual behavior, is highly dependent on testosterone. The MePD
volume is 1.5 times greater in male rats than in females. Structural plasticity in
the adult MePD appears to be mediated through activation of both ARs and
ERs. Testosterone treatment increased MePD soma size, but did not affect
volume. Interestingly, MePD volumes are greater in the right hemisphere than
the left. This laterality in MePD volume is not found in females, suggesting that
its presence may depend on some masculinizing factor [116].
The male brain engineering is not only related to the male’s ability to have
high sexual drive and right hemispheric dimorphism, but it also affects the
brain’s biological clock! The vasoactive intestinal polypeptide (VIP)‐containing
subnucleus of the suprachiasmatic (SCN) is twice as large in men as in women.
In addition, the vasopressin‐containing subnucleus of the SCN has a different
shape in men than in women. Sexual orientation has also been correlated with
the size of the human SCN. The vasopressin subnucleus of the SCN in homo­
sexual men has been found to be 1.7 times larger and contain twice as many
cells compared with heterosexual men.
The ventromedial hypothalamus (VMH) is another sexually differentiated
region that is involved in sexual and parental behaviors. VMH volume and
number of neurons are greater in males than in females, and males also have a

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