Steroid hormones, such as testosterone, have dramatic effects on brain development.
Many scientists use rats as model systems in studying these effects.
As a male rat develops, his testes secrete the hormone testosterone,
which masculinizes the nervous system and other body tissues.
In females, little testosterone is present, and the nervous system
develops along a female pathway.
The sex differences in the developing nervous systems
direct sex-specific behaviors in adults.
These behaviors serve as indicators of early hormone exposure.
A key behavior of females during copulation is lordosis,
a posture in which she arches her back and moves her tail to one side.
Lordosis allows the male to insert his penis,
which is a male-specific behavior called intromission.
The development of the nervous system can be permanently altered
by the administration of steroids.
If a female rat is exposed to testosterone early in development,
her nervous system becomes masculinized.
As adults, these females have a loss or reduction in lordosis behavior.
Testosterone, therefore, has a permanent organizational effect on the nervous system.
It may seem logical that testosterone would masculinize the nervous system
of a developing female, but what would you expect estrogen to do?
It turns out that estrogen also induces masculinization.
As adults, females exposed to estrogen as young pups
have a reduction in lordosis behavior.
To understand why testosterone and estrogen have similar effects,
let us examine the aromatization hypothesis.
Our focus is at the cellular level,
and the large circular structure represents a neural cell
in the brain of a developing animal.
Testosterone from the testes reaches the brain,
passes through the blood–brain barrier,
and slips through the plasma membrane of the neuron.
In the neuron, an enzyme called aromatase converts testosterone into estradiol,
which is an estrogen.
Estradiol binds to estrogen receptors in the cell.
The hormone–receptor complex enters the nucleus,
where it binds to DNA and turns some genes on and others off.
This change in gene expression occurs in neurons in
various areas of the nervous system, resulting in masculinization.
The aromatization hypothesis explains why treatment with either testosterone
or estrogen masculinizes the nervous system.
Free estrogen enters neurons, binds to estrogen receptors,
and triggers the same changes in gene expression as seen with testosterone.
In the case of estrogen, however, aromatase is not necessary
for the masculinization to occur.
It is important to note that the pregnant mother produces estrogen,
and that this estrogen passes through the placenta
and enters the bloodstream of the fetus.
However, this estrogen does not masculinize the fetus.
The fetus produces a protein called an alpha-fetoprotein,
which binds to estrogens and prevents them from entering the brain.
When a developing female rat is exposed to extra estrogen in an experimental study,
presumably there is not enough alpha-fetoprotein available
to bind to all the circulating estrogen.
Thus, some of this estrogen is able to enter the neuron
and trigger masculinization.