A new study finds that male rat fetuses exposed to aspirin have a less masculinized brain and a reduced sex drive as adults. The results reveal a surprise twist in how testosterone makes males out of fetal rats.
Early in development, the mammalian brain is neither male nor female. When a male fetus begins making testosterone, its brain responds by, among other things, tripling the number of neurons in the region called the preoptic area (POA). In adulthood, this part of the brain revs up when a male runs into a ready and willing female.
For decades, scientists have been trying to determine exactly
how testosterone causes such masculinizing changes in the brain.
Most researchers have focused on sex hormones, but a study that
suggested prostaglandins--molecules better known for their role in
inflammation--might be involved in setting up differences between
the sexes during puberty caught the attention of behavioral
neuroscientist Margaret McCarthy and her graduate student Stuart
Amateau, both at the University of Maryland in Baltimore. They
wondered whether the compounds might also play a role in fetal
development.Amateau gave newborn male rats either a prostaglandin
called E2 or a prostaglandin inhibitor. When the rats reached
sexual maturity at 55 days old, the researchers tested their
interest in copulation. Male rats who received the inhibitor took
20 times longer than nontreated males or those who had been treated
with E2 to get around to mating with a receptive female. Once they
did, they mounted about seven times less frequently, they report
online 24 May in Nature Neuroscience. This suggested that E2
was key to masculinization of the brain. The inhibited rats grew
significantly fewer POA neurons as well.In a second set of
experiments, Amateau gave baby aspirin--which inhibits
prostaglandins generally--to pregnant rats in their drinking water,
for a week before and a week after they gave birth, while they were
nursing. Sons of these mothers took about twice as long as normal
to respond to receptive females as did untreated males. McCarthy
says it's too early to say what effect aspirin might have on human
males, but other researchers are looking into it."The results help
[scientists] zero in on the molecular consequences of steroids in
the brain," says neuroscientist Marc Breedlove of Michigan State
University, East Lansing. Those consequences, he adds, have a
surprise player. "We're used to thinking of prostaglandins as
involved in inflammation. It's a surprise to think of them as
messengers in the brain."Related site
McCarthy's
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