Early Career Scientist Studies Linkages between Brain and Reproduction

June 25, 2013

by Jennifer Anderson 

We all go through puberty--but what happens in the brain to make the whole process possible?  And why do girls sexually mature before boys, and what sets the clock so that puberty always is at about the same age for each sex?

“We have clues, but we don’t know the major drivers,” says Alexander (Sasha) Kauffman, PhD, who studies reproductive neuroendocrinology out of his lab in San Diego.  “Something is happening in the brain to cause this life-changing event.”

Back up 42 years: in 1977 two scientists shared the Nobel Prize for their discovery of a brain hormone known as GnRH--gonadotropin releasing hormone--and its role in “turning on” reproduction, so females ovulate and produce eggs and males make sperm and testosterone.  “All of reproduction is dependent on GnRH,” Kauffman explains.

S Kauffman Quote Box.jpgBut what triggers GnRH?  Scientists hypothesize regulatory factors are at work in the brain, signaling GnRH to launch puberty.  “We’re trying to figure out what are these things in the brain that regulate GnRH and, hence, reproduction,” he says.

Enter “kisspeptin,” a neuropeptide produced by neurons in several places in the brain and responsible for sending signals to stimulate GnRH neurons.  In 2003 scientists learned that humans and mice with kisspeptin gene mutations have problems with sexual maturation and infertility. 

A “flurry of scientific activity” ensued, Kauffman states in a research report, uncovering kisspeptin’s essential role in sending the signal to GnRH to push the body into puberty and start the reproductive process.  “It is now clear that hypothalamic kisspeptin directly activates GnRH neurons to stimulate the reproductive axis,” he explains in the paper.

Still, no one knows how kisspeptin does this, why, or even exactly when?  And then we get into the Third Man Argument: What regulatory factor signals to kisspeptin neurons, and so on?

Kauffman describes the brain as an “undiscovered country”--a place where, despite all the research to date and thousands of published papers—we still know so little.  But the scientific field is not dissuaded.  Just look at the interest now in puberty and reproduction.  

“I feel like the kisspeptin field has tripled in the past five years,” he says, adding that he collaborates not only with labs in the United States but also in Europe, Australia and South America.  “It’s a hot topic within neuroendocrinology.”

Since all mammals (not to mention fish and frogs) have kisspeptin, much of what we learn is coming from mouse models.  “Puberty comes earlier in girls, and this is also true for mice,” Kauffman says.  From these rodents, research also has uncovered intriguing differences between male and female brains, not only in the sizes of specific parts of the brain but also the numbers of various proteins and the types of genes expressed.

Kisspeptin itself is different in the brains of males and females, Kauffman says.  “It doesn’t mean that’s the reason for the sex difference in puberty timing,” he says.  “But it’s a potential link.”

Then there are all the related questions:  Why is it that some people never enter puberty? Conversely, why do some children have “precocious puberty,” growing breasts or body hair at a young and inappropriate age?   And why are some adults unable to reproduce?  Infertility is on the rise in America, and so are obesity, diabetes and other illnesses affecting fertility.

And by the way, what turns off reproduction as we get older?

“I find it fascinating,” Kauffman says.  “The whole reproduction field is just exploding.”

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Sasha Kauffman was recently honored with the Federation of Associations in Behavioral & Brain Sciences (FABBS) Foundation Early Career Investigator Award during the annual meeting of the Society for Behavioral Neuroendocrinology.

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