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Aspirin Kills More Than Pain for Male Rats

24 May 2004 (All day)
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Bitter pill. In rats, aspirin seems to reduce masculinization of the brain.

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 site

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