206 Autism and Exposure to Environmental Chemicals
higher concentration of ARs in the VMH than do females. The VMH contains
four morphologically distinct regions, including the anterior (VMHa), dorso
medial (VMHdm), ventrolateral (VMHvl), and central (VMHc) subdivisions,
which have distinct connectivity patterns to other brain regions and may affect
a variety of functions (Figure 7.12). In a recent study, volume and neuronal
numbers of the entire VMH and its four subdivisions were compared between
males and females, and, confirming earlier findings, the overall VMH volume
was greater in males than in females.
The bed nucleus of the stria terminalis (BNST) is a center of integration for
limbic information and balance monitoring. The BNST, sometimes referred to
as the extended amygdala, is located in the basal forebrain and is a sexually
dimorphic structure comprised of between 12 and 18 subnuclei. These subnu
clei are rich with distinct neuronal subpopulations of receptors, neurotrans
mitters, transporters and proteins. The BNST is important in a range of
behaviors such as the stress response, extended duration fear states, and social
behavior, which are all crucial determinants of dysfunction in human psychiat
ric diseases [117].
A portion of this region, the posteromedial nucleus of the bed nucleus of the
stria terminalis (BSTMPM) exhibits several sexual dimorphisms, including
greater AR density and regional volume in males compared with females.
Interestingly, there was a sex difference in BSTMPM volume in both the left
and right hemisphere (males > females), where volume was increased in males
compared with females only in the left hemisphere. These results suggest that,
as in the MePD, ARs normally contribute to the full masculinization of the
BSTMPM in males [117].
AVP innervation of the septal area (including the BST), which plays a role in
pair bonding, parental and aggressive behavior [118], is also sexually differenti
ated. AVP innervation of this area is greater in males than in females and is
dependent upon androgens in both early development and adulthood.
The locus coeruleus (LC), a brainstem nucleus implicated in the physiological
response to stress and panic, is an example of a sexual dimorphism in which
females show a larger volume and a greater number of neurons than do males.
This dimorphism appears to be under the control of both testicular and ovar
ian hormones, with testicular steroids decreasing and ovarian steroids increas
ing growth and survival of LC cells. The hippocampus is another sexually
dimorphic area of the brain in which males show a greater overall volume than
females. One area of the hippocampus, the dentate gyrus, is sexually dimor
phic in some strains of mice in which males show a greater number, size, and
density of cells within this region [119].
As we have explained above, many parts of male brain are larger and have
more compact neuronal mass than females, identifying specific regions that
have a unique role in male behavior. Therefore, along with the emerging role of
high levels of testosterone in weeks 8–24 of gestation and expression of the AR