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Hormone that may launch puberty is discovered

By Ronald Kotulak, Chicago Tribune
June 22, 2006

Scientists are still a long way from figuring out what women and men really want, but they are getting a lot closer to understanding what makes their brains so different.

That women and men think differently has little to do with whether they played with dolls or trucks. The differences, researchers are beginning to discover, appear to have a lot more to do with how powerful hormones wire the female and male brain during early development and later in life.

Among the newest findings: A previously unknown hormone appears to launch puberty's sexual and mental transformation; growth hormone is made in the brain's memory center at rates up to twice as high in females as in males; and the brain's hot button for emotions, the amygdala, is wired to different parts of the brain in women and men.

Scientists hope the findings may help explain such mysteries as why females are often more verbal, more socially empathetic, more nurturing and more susceptible to depression, while males tend to be more aggressive, more outdoorsy, more focused on things than people and more vulnerable to alcohol and drug addiction.

“Males and females look different, we act different, so of course our brains are different,” said Rutgers University psychologist Tracey Shors, who is studying the effects of growth hormone on the brain. “Sex hormones along with stress and growth hormones change the brain's anatomy, and in that way you change behavior, your ability to think and learn.”

Sex differences begin with the X and Y sex chromosomes a person is born with. But scientists now believe that whether the brain and nervous system are wired as female or male depends a lot on the early influence of estrogen, the so-called female hormone, or testosterone, the male hormone.

The brain's sexual identity is first established when those hormones are briefly released before and shortly after birth, which may influence a child's preference for dolls or trucks.

“There's a peak of testosterone in males at birth that's very important for future sexual behavior,” said Dr. Sophie Messager of Paradigm Therapeutics in Cambridge, England. “If you block that, the male rats behave like females for the rest of their life.”

The sex hormones then lie dormant until they get turned on again in puberty to make the body ready for reproduction.

That is where a recently discovered hormone called kisspeptin comes in.

Created in the brain, kisspeptin unleashes a cascade of hormones that race down to the gonads – ovaries in females and testes in males.

There they stimulate the production of estrogen or testosterone, starting the physical transformations of puberty. Messager proved in animals that blocking kisspeptin prevented those changes from happening.

But there is another target for this activity: the brain. The hormonal down rush kicked off by kisspeptin comes full circle when estrogen and testosterone travel back to the brain, imprinting neural circuits with female and male characteristics, Messager said.

Animal studies show that genetic females will behave like males if their estrogen is blocked and replaced by testosterone. Genetic males, in turn, act like females if their testosterone is knocked out.

Until kisspeptin was discovered, scientists had generally accepted the idea that sex differences were centered in the hypothalamus, a small organ on the underside of the brain. It was thought that the hypothalamus originated the flow of hormones that start puberty, determine male and female physical characteristics and orchestrate mating behavior.

“The bias of mainstream neuroscience for the last 25 years has been, 'OK, sure there's some sex differences way down deep in the brain in this little structure called the hypothalamus, but otherwise, the brains of men and women were pretty much the same, 'T” said Larry Cahill, a neurobiologist at UC Irvine.

“That was wrong, as wrong as could be.”

One example lies in the amygdala, the organ that interprets the emotional content of an experience, affecting what people remember. Located deep in the brain on both sides, the amygdala amplifies memories that are pleasant or frightening. It tells the hippocampus, where memories are put together to be stored, which memories need to be most tightly locked in place.

Cahill and his colleagues found that the amygdala works differently in men and women. He found that when men and women watched the same emotional movie, the right side of the amygdala was more active in men, and the left amygdala was more active in women.

The right amygdala is more in tune to the outside environment, communicating with the visual cortex, which controls vision, and the striatum, which coordinates motor actions. These processes are thought to be key to spatial orientation – knowing how to negotiate your surroundings, as in hunting.

The left amygdala is concentrated more on the inner environment of the body and the hypothalamus' regulation of the body's metabolic and autonomic activities. Scientists speculate that this is important for the female capacity for nurturing.

One possible explanation for why women tend to be less aggressive than men is that they may be better able to filter out overly arousing feelings. The front part of the brain, which controls emotions, is bigger in women than in men when compared with the size of the amygdala, where experiences get their emotional charge.

That difference may be why women are less prone than men to fly off the handle, Cahill said.

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