This was originally mentioned by Kofi and I found it interesting
enough to be posted in full text. How arachidonic acid metabolites
can rewire the brain when applied early enough ... Looks like
testosterone effect but it is actually mediated by PGE2.
Taka

Aspirin changes sexual behaviour of rats

May 2004, James Randerson
Aspirin and other anti-inflammatory drugs given to newborn rats change
their sexual behaviour later in life. The drugs interfere with the
brain's sex-specific development, suggesting that they may also affect
equivalent mechanisms in humans.

In theory, mothers taking such drugs might pass on high levels to
their baby via the placenta. The list includes aspirin, paracetamol
(tylenol) and indomethacin (indocin), which prevents premature labour.

But the researchers caution that, until similar effects have been
found in people, expectant mothers should not change their use of
medication.

"I don't want to panic pregnant women," says Margaret McCarthy, who
carried out the study at the University of Maryland, Baltimore, US,
with her colleague Stuart Amateau. She says women are already advised
to avoid taking unnecessary drugs.

"I don't think we can say anything about humans based on this," says
Melissa Hines an expert in the neural basis of sexual behaviour at
City University in London, UK. She points out that hormonal changes
associated with maternal stress in rats have been linked to changes in
the sexual behaviour of their offspring - but the same changes do not
happen in humans.

Black box
The work is also a significant advance in the fundamental
understanding of how testosterone masculinises the brain, says Marc
Breedlove, a neuroscientist at Michigan State University in East
Lansing, US. "What steroids do is currently something of a black box,"
he says.

In particular, McCarthy and Amateau identified a signalling molecule
that links the testosterone signal - telling the brain to "be a man" -
to changes in the brain.

The discovery of the molecule, called prostaglandin-E2 (PGE2), was a
surprise because prostaglandins are usually associated with pain
mediation and the body's inflammatory response. "There was no
indication that they were involved in brain development or sex
specific effects," says McCarthy.

Lowered libido
McCarthy and Amateau injected newborn male and female rats with either
indomethicin, a powerful blocker of PGE2 production, or PGE2 itself.
Male rats given indomethicin had a much lower libido than those given
a placebo when they were presented with females as adults.

The research team also found changes in a region of the brain called
the preoptic area, which is implicated in both male and female sexual
behaviour. The neurons had fewer connections to other nerve cells.

In contrast, females given PGE2 behaved more like males as adults.
They were more likely than control rats to mount and attempt to
copulate with other females. But the researchers stress that their
experiments did not give the rats a choice between the sexes and so do
not have implications for sexual orientation.

McCarthy says the next step will be to carry out similar experiments
with primates. If the results are similar then it is much more likely
that humans will be affected in the same way.

Also, a long-term epidemiological study of 15,000 mothers and their
children, based in Bristol, UK, may be able to detect the effect in
humans.

Journal reference: Nature Neuroscience (DOI: 10.1038/nn1254)