Developmental
cell death and sexual differentiation
in mice and rats.
 A
large number of sex differences have
been described in the nervous systems
of mammals. In most cases, sex differences
in neural structure or neurochemistry
can be traced to the actions of the
steroid hormone, testosterone, produced
by the testes of perinatal males.
For example, testosterone creates
sex differences in neuron number by
controlling developmental cell death.
Throughout the nervous system, many
more neurons are born than will survive
into adulthood, and “excess”
neurons die during a period of naturally
occurring cell death. Testosterone
(or one of its hormonal metabolites)
decreases neuronal cell death in some
areas of the brain and spinal cord,
while increasing cell death in others.
We are investigating the cell and
molecular mechanisms underlying these
actions of testosterone. Specifically,
we have been focusing on neurotrophic
factors, and proteins of the Bcl-2
family as likely mediators of hormonally-controlled
cell death. (For more information,
see 
Xu
et al., 2001,
Forger
et al., 2004 and Jacob
et al., 2005.)
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Naked
mole-rats are subterranean rodents
that live in colonies consisting of
60-80 individuals. Their social structure
is highly unusual, and has been described
as “eusocial.” Only a
single female (the queen), and 1-3
males breed. All other individuals,
known as subordinates, are reproductively
suppressed and help in colony maintenance
and rearing of the young. Subordinates
exhibit no sex differences in behavior
and even the external genitalia are
remarkably undifferentiated. Subordinates
never exhibit sexual behavior, despite
life spans that can exceed 20 years,
but become reproductively active if
removed from their colonies and paired
with an opposite sex mate. This raises
the question of the degree to which
sexual differentiation has occurred
in subordinate naked mole-rats. In
collaboration with Bruce Goldman at
the University of Connecticut, we
are examining the nervous systems
of subordinate and breeding naked
mole-rats. We find that most neural
sex differences are absent in naked
mole-rats. Instead, changes in brain
and spinal cord morphology and neurochemistry
are associated with breeding status.
(For further reading, see 
Spotted
hyenas have fascinated biologists
for centuries, primarily because of
the extreme virilization of the female
genitalia. There is no external vagina,
and female spotted hyenas urinate,
copulate, and give birth through a
single urogenital canal that traverses
a “phallus” closely resembling
the male’s penis. In addition,
a number of other physical and behavioral
traits are “masculinized”
in female spotted hyenas. This virilization
of anatomy and behavior is thought
to be due to the fact that spotted
hyena fetuses of both sexes are exposed
to elevated levels of testosterone,
formed in the placenta from maternally
derived pro-hormones. In collaboration
with Steve Glickman at the University
of California, we have been examining
the nervous system of spotted hyenas.
Specifically, we are asking whether
sex differences found in other mammals
are present in spotted hyenas. (For
more information, see