Source: Observer
Date: 31 July 2005

Chemical kiss turns kids into adolescents

Robin McKie, science editor

It is sealed with a kiss. Researchers have found that a protein called kisspeptin triggers the cascade of biochemical changes that leads to puberty and turns children into hormonally challenged adolescents.

The discovery raises hopes of understanding one of human biology's fundamental processes, when a young person's body is propelled towards sexual maturity, turning a normal, happy child into a sulking, spotty teenager.

More importantly, the finding could lead to the development of drugs to block the premature onset of sexuality in very young children.

The discovery also raises prospects of developing new treatments for breast and prostate cancer. These tumours are nourished by sex hormones that are in turn controlled by kisspeptin.

'It is very rare that a completely new area of physiology is opened up like this,' said Mark Carlto, of Paradigm Therapeutics, Cambridge. 'It is enormously exciting and potentially very important.'

Scientists have known for years that puberty begins when a child's brain orders the release of hormones that cascade through the body. This leads to the maturing of testes in boys and ovaries in girls.

'We have found the exact process involves kisspeptin fitting into a receptor on the surface of cells in one part of the brain,' said Professor Tony Plant of the University of Pittsburgh. 'This causes the cell to send out a signal to the pituitary gland which releases hormones. It begins, literally, with a kiss.'

Puberty is still one of biology's greatest mysteries, nevertheless. 'Sex hormones are actually secreted in the foetus and new-born baby,' said Plant. 'Then production is suspended not long after birth for more than a decade. Then it is abruptly restarted.'

Many scientists believe this delay has evolved to give youngsters a chance to learn and assimilate cultural values without being distracted by sexual urges. Puberty may also give the body a chance to store enough energy to support reproduction later in life.

'As to the exact timing of puberty's onset, that is either due to a biological clock in the brain starting to pump out kisspeptin at a precisely determined time, or some sort of internal meter decides when the body is in the right condition for sexual maturity to begin,' said Plant.

'We don't know which. However, the finding of kisspeptin's basic role in puberty gives us a way to investigate which of these two theories is right.'

The discovery also suggests several key medical applications. The first concerns breast and prostate cancers. When these tumours develop, they are nurtured by the sex hormones oestrogen and testosterone. 'If we could turn off the production of these hormones, the tumours should shrivel and die,' said Mark Carlton. 'That could be done by blocking the brain cell receptor that kisspeptin fits into. It would be like putting chewing gum in a car's ignition.

'We are searching through libraries of chemicals for candidates that could block brain cell receptors and stop sex hormone release. It could take years to find one but the potential is immense.'

In addition, chemicals to block kisspeptin's role in switching on sexual hormones could be vital in preventing children reaching puberty when they are only five or six years old, as occurs in a number of different conditions involving precocious sexual development. Treatments for these exist but can involve painful regimes of injections. New oral treatments could be developed.

Similarly, for young people who suffer from conditions in which puberty does not start in their teenage years, it should be possible to administer kisspeptin derivatives that will trigger the condition artificially.

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