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Steroid hormones have dramatic effects on
the development of the mammalian brain and
on the display of subsequent behavior in adulthood.
In response to hormonal exposure, the fetal
brain undergoes sexual differentiation, resulting
in differences in neural structure and function
between males and females. Previous research
has focused on the effects of testosterone
from the fetal testes in the development of
sex differences in brain function. In addition
to hormones from fetal origin, fetuses and
neonates are exposed to circulating maternal
hormones, which readily cross the placenta
and are presumably present in mother's milk.
In particular, levels of the maternal hormone,
progesterone are present in extremely high
levels during pregnancy.
My research examines the effects of the
maternal/fetal interaction on neural development,
specifically the effects of maternal progesterone
on the development of sex differences in
the brain and behavior. One way in which
steroid hormones act in neurons is through
interactions with nuclear steroid receptors.
Therefore, in order to examine when the
developing brain first becomes sensitive
to progesterone, we have used immunocytochemistry
to detect the expression of progesterone
receptors in both the fetal and neonatal
brain.
Recent work in my lab has revealed that
certain areas of the fetal rat brain express
progesterone receptor well before birth.
The expression of progestin receptor (PR-ir)
in the medial preoptic nucleus (MPN) of
rats on the day of birth is high in males
but virtually absent in females. The MPN
of rats is sexually dimorphic and mediates
several sexually differentiated behaviors
in adulthood. These results suggest that
the brain of the male fetus may be more
sensitive to maternal hormones than that
of females and that progesterone may play
a critical and previously overlooked role
in the sexual differentiation of the brain.
With this work we have revealed that a
novel role of the mother in the development
of the fetal CNS must be considered. We
are currently examining what hormonal signals
trigger the differential expression of progesterone
receptor in male and female fetal brains
and over what periods of development this
sex difference exists. In addition, we are
very interested in pursuing what role progesterone
and its receptor play in mechanisms such
as neuronal differentiation, cell migration,
cell death and other cellular events known
to contribute to sex differences in the
CNS. This research can then be extended
to examine the role of maternal hormones
in the development of sexually differentiated
behaviors such as sexual behavior and maternal
behavior.
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