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| Archive : Fall
2006 |
FROM BACH TO BEDOUINS, MANY STONES WERE TURNED IN SEARCH OF CLUES TO HOW PUBERTY BEGINS:
An eighteenth-century choir // A gene that “kisses” // Harry Potter // Saudi cousins // Songbirds //
And, of course,
pimply faced adolescents.
To Grow Hairy [page 3]
 By Stephen S. Hall |
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The initiation of puberty, at least in this instance, required the activity of a gene occupying a small segment on human chromosome 19. The gene contains the instructions for a protein, GPR54, which is a receptor—a kind of biochemical satellite dish—sitting on the surface of certain cells in the hypothalamus. In 2003, using the DNA of the original six Saudi patients, Crowley, endocrinologist Stephanie Seminara and others within their group, along with researchers in England and Kuwait, figured out that a tiny defect in a single bead in the string of amino acids that make GPR54 was enough to warp its antenna, obliterating its ability to receive signals.
By coincidence, a biotech company in England working with Crowley’s group had isolated and systematically examined dozens of unknown genes belonging to this same family of receptors and had named each uncharacterized gene after a famous orphan. Thus, it turned out that the company had independently identified the gene responsible for making GPR54 and dubbed it Harry Potter. Crowley’s response? “I told them they gave it the wrong name,” he says. “They should have named it the Peter Pan gene because these kids never grow up.”
What molecular message did the brain fail to receive when the GPR54 receptor wobbled like a wind-tossed satellite dish? Last year Crowley, along with researchers at the University of Pittsburgh and the Oregon National Primate Research Center in Beaverton, provided the beginnings of an answer. Specifically, they reported that puberty begins when another brain protein, with the suggestive name kisspeptin, “kisses” the GPR54 receptor and flips the switch on puberty.
What triggers kisspeptin? No one knows—yet. But as in other areas of growth biology, the ultimate answer, at least in part, appears to come from the environment. Cheryl L. Sisk, a psychologist at Michigan State University, and reproductive science researcher Douglas L. Foster of the University of Michigan, in a recent review article in Nature Neuroscience, pointed out that for puberty to begin, “the individual must perceive whether it has grown sufficiently (through metabolic cues), what its relationship is to other individuals (through social cues), and whether conditions are optimal to begin the reproductive process (through environmental cues).” Those are a lot of cues coming from the outside world, and probably a lot of neural circuitry to integrate all those inputs into a single, coherent message.
The neural makeover that puberty unleashes in the brain involves not the creation of new brain mass, but rather the sculpting and grooming of what is already there. In 1992 a research team headed by Judith Rapaport at the National Institute of Mental Health (NIMH) in Bethesda, Md., began tracking this neural development in more than 1,000 children. She and her colleagues have since reported that there is a “second wave of neural development” during the teenage years, even as the brain simultaneously shrinks.
“The number of nerve cells is not changing,” says Jay N. Giedd, a member of the NIMH team, “but they are growing more connections. My best working hypothesis is that in children the nerve connections are bushier, but after puberty the advance is made by pruning. So even though the bush is skinnier, the quality is better. I guess the best analogy is to Michelangelo and a block of marble, where the quality improves as you take things away. That’s what experience teaches—what to keep and what to throw away.” |
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Photo by H. Armstrong Roberts/ ClassicStock |
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