Men’s brains, female sex hormones, and the nature of scientific discovery.

By Christine Jasoni 27/07/2013

Boys will be boys… if their brains get enough female sex hormones, that is.

Gorgeous guy walks into a cafe. Heads spin ‘round. The girls smile coyly, and giggle amongst themselves – he’s so cute. The guys frown, brandishing muscles or harsh words– who does that guy think he is anyway?

The curious thing about this is that even though everyone sees the exact same thing (the handsome chap), somehow the female brain produces female responses, whereas the male brain produces male responses. From a neuroscientists perspective, this scenario is almost even funny, because despite their dissimilarity, the two responses are produced from the same areas within the brain. That’s right – the nerve cells themselves appear to function differently in male versus female brains (1, 4).

The reason for this has to do with the hormones that our brains were exposed to as they were forming. As we know, adult males make testosterone – it’s what makes them hairy with deep voices. But the reason males and females also show behaviours that are unique to their sex has to do with differences in their brains; differences that came about very early in life, and which also involve testosterone (1). Let’s have a closer look.

In very young males, soon after birth, testosterone is made by the testes, and the blood system carries it to the brain. When it gets there, it is transformed into another substance, estrogen, that acts on certain nerve cells and gives them important instructions – like whether to make more of themselves and how to connect with other parts of the brain (1, 3, 4, 5). Females don’t have testosterone, their brains don’t get this same education, and so they develop differently. The upshot is that male and female brains are different – not massively different, not different everywhere – just in a few places that control behaviours, like sex (1) and aggression (6), that are unique to either males or females.

But hang on a minute, females have estrogen, and if estrogen is the molecule that is transmitting the testosterone signal into the male brain, what’s going on? Why doesn’t the estrogen that’s around in females go to their young brains and act just like the estrogen that has been converted from testosterone in the male brains? Turns out its all about timing and amounts. In males massive amounts of testosterone are produced over a short time early in life, in what we call the ‘neonatal testosterone surge’ (7). So for a brief period right after birth, the male has heaps of testosterone, and his brain is swimming in estrogen. Meanwhile, young females make a constant low amount of estrogen, which never gets to high enough amounts to get into the brain.

Back to the young male brain. At this point you may be wondering, as the scientists did: if it’s really testosterone, what happens if we take it away from the young male? Does he become like a female? Using experimental animals, researchers changed the amount of testosterone that the young brain was exposed to. When they did this they found that when the young male was deprived of testosterone, his brain looked female and he behaved in some ways like a female, showing female-like mating behaviour, and reduced aggression (1). I say ‘in some ways’ because the reversal in brain and behaviour is not 100%. In case you’re wondering, the opposite experiments have also been done in females. By adding testosterone to young females, their brains look more like a male’s and they show male-like mating behaviour and increased aggression. But again the transformation is not 100%. This tells us that there is probably something else going on in the young brains that is important to make male and female brains and behaviours different.

Research published last week (2) reveals that the female hormone progesterone is also important for crafting male and female brains and behaviours. That’s right: another female hormone influencing the male brain. When the nerve cells that respond to progesterone are removed from the female brain their sexual behaviour in response to males is reduced. When these same cells are eliminated from male brains, the males show reduced sexual behaviour and are less aggressive. Thus, when progesterone signals don’t work, whether male or female, the animals seem to lose their sex-specific mating behaviours, but only males show changes in aggression. This is different from the experiments that manipulated testosterone, which seem more to reverse sex behaviour and aggression in both males and females. How the progesterone story fits-in remains unclear, but compelling new experiments lie ahead for putting all of the players in order so that we can understand the structure and function of neural cells and circuits that underpin male and female behaviour.

There are exciting further questions too, many of which you’ve probably been wondering already, and which Neuroscientists are working on right this minute. How do these brain circuits, laid down in early life, change when our bodies (and our hormones) change at puberty? How much could changes to these early circuits contribute to homosexuality? Why are some mental illnesses, such as autism spectrum disorders, or behavioural difficulties, such as risk-taking, more prevalent in one sex compared to the other. Important questions, the answers to which will be critical to improving our health and wellbeing throughout life.

I hope that this brief overview also serves as an illustration of the scientific process: Discovery happens in small steps. With each step we become more certain about one thing, only to reveal heaps more questions about others. We ask questions, and make our best guess, our hypothesis, based on the information we have at hand. For example, we once thought that testosterone was the important thing to make male brains male. And then we do experiments to see whether we’re right or not. Quite often we find the unexpected – it’s actually estrogen converted from testosterone – causing us to revise our view of the past. It’s really very much like revising history when skeletons in the closet are revealed. Which means that it’s something that we all do whether we realise it or not – the happy conclusion is that there’s at least a little scientist in all of us.