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Ready or Not

Kisspeptin, named after a sweet chocolate treat, jumpstarts puberty. But when does the gene that produces it know when to start?

By Cathryn Delude // Fall 2006
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The name of the gene that codes for kisspeptin, first identified by cancer researchers in Hershey, Pa., land of the eponymous chocolate Kisses, became doubly apt with the discovery of the gene’s role in puberty. Once awakened in neurons deep within the hypothalamus, the Kiss1 gene begins to churn out kisspeptin, which sets in motion the production of sex hormones, ushering in sexual maturity.

The Kiss1 system, says Stephanie Seminara, a Massachusetts General Hospital endocrinologist who played a lead role in its discovery, “is pivotal, indispensable and potent.” But it’s not the beginning of the story: What tells Kiss1 when the time is ripe?

Part of the answer is hormones, which report to the brain the status of all body systems. A main indicator of a child’s metabolic resources, for example, is a hormone called leptin. Secreted by body fat, it reveals how much energy the body has stored. (The body needs enough energy resources to support fertility and, in girls, pregnancy. That’s why malnourishment, anorexia or extreme exercise can delay puberty or stop menstruation.) Among its other duties, leptin activates the Kiss1 gene in selected neurons. Thus, very low body fat causes low leptin levels and, consequently, low kisspeptin and sex hormone levels.

Recent research points to a potential therapy to counter such problems. Scientists have known that giving leptin to underfed animals can start the production of sex hormones. Now, though, researchers have discovered that giving the animals kisspeptin alone can also launch puberty. Studies by Robert Steiner, professor of obstetrics and gynecology and physiology and biophysics at the University of Washington, suggest that leptin works upstream of kisspeptin, binding to receptors on Kiss1 neurons and directly activating the gene to produce kisspeptin. Giving kisspeptin appears to trump leptin by acting further along in the process, a finding that could lead to new treatments for reproductive disorders and hormonal contraceptives.

Seminara cautions, however, that there is still much work ahead before any such treatment becomes a reality. “People always look for an A to B to C pathway,” she says. “That’s too simplistic when we’re talking about puberty.

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