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26 September 2013

The teenage hormone that triggers puberty and prevents cancer

The appropriately named kisspeptin was discovered by accident, and has some surprising effects.

By Michael Brooks

Whatever your parents told you, it’s not about the birds and the bees. Ultimately, reproduction seems to be about a protein molecule called kisspeptin. The name has nothing to do with foreplay, however. Kisspeptin was discovered in Hershey, Pennsylvania, and its name comes from the town’s other great research success: Hershey’s Kisses chocolates.

At some point, most people’s brain starts to secrete kisspeptin; when it does, the hypothalamus begins to produce a chemical called gonadotropin-releasing hormone, or GnRH. Written down, it looks like a teenage grunt and that’s what it leads to. GnRH release is a crucial moment at the beginning of puberty. It brings about the secretion of hormones that start egg or sperm production and create the characteristic signs of sexual maturity.

On 12 September, the King’s College London professor Kevin O’Byrne discussed the “enigma” of GnRH at a conference at the University of Bristol. The central enigma is the unanswered question of what kicks off puberty – we still don’t know what activates kisspeptin to release GnRH.

It seems to have something to do with the brain’s monitoring of stress and nutrition. Without good fat reserves and a relaxed demeanour, the chemical sages won’t let you enter the trials of reproduction. That’s why girls suffering from anorexia can experience disrupted menstruation.

Kisspeptin’s role in puberty was discovered by accident when researchers were looking at its anti-cancer properties. Controlling the teenage brain is not the only thing it can do. GnRH is now used as a part of some cancer treatment routines because it stops the production of oestrogen, a hormone that seems to play a role in stimulating tumour growth.

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Here’s another clue: some of the ugliest rodents on the planet, known as “naked mole rats”, are awash with kisspeptin – and they don’t get cancer.

Most animals have levels of kisspeptin neurons that vary according to sex as well as reproductive state. New research shows that naked mole rats have high kisspeptin and GnRH levels no matter what their readiness for reproduction.

That is particularly odd because, despite these high levels of kisspeptin, most naked mole rats don’t develop the ability to breed. Like some species of bee, naked mole rats live in colonies in which only a queen and a few consorts develop the ability to reproduce. The rest are workers that remain sterile all their lives. And those are long lives.

Their extraordinary resistance to developing cancers makes naked mole rats the longestliving rodents. Mice and rats typically live for two or three years; naked mole rats often live for two decades or more. Understanding what kisspeptin does for the naked mole rat could assist our fight against the ravages of ageing.

However, our slowly increasing grasp of kisspeptin and GnRH is causing a dilemma. The age at which human beings hit puberty is falling – on average, it has fallen by five years since 1920. It’s less of a problem for boys than for girls, for whom “precocious puberty” is linked with an increased risk of breast cancer, mental disorders and, in later life, polycystic ovary syndrome.

That raises the question of whether we should intervene. There’s still a lot we don’t know but research has shown that an injection of kisspeptin kicks off puberty artificially. More usefully, drugs that block kisspeptin prevent puberty from starting and doctors are starting to intervene in the most extreme cases of precocious puberty. Some see this as a risky thing to do when we have no long-term data on the outcome.

This new branch of science might not yet have hit puberty but it is already starting to give us trouble.