Science - May 26, 2005

‘Fat’ hormone gets puberty going

The hormone leptin ensures that animals enter puberty, according to a PhD researcher who did tests with young rats.

Leptin is a hormone that reduces appetite. If an animal gets enough to eat and its fat layers grow, it starts producing more of the hormone. Leptin is produced by fat cells, and the faster these grow the more leptin they produce. In this way fat cells regulate appetite. Much of the research on leptin is fuelled by the hope that leptin might be the answer to the current obesity epidemic.

Saeed Zeinoaldini, who was working at the Human and Animal Physiology group, however was interested in a different aspect of leptin. He started with the question whether the hormone perhaps is responsible for determining the moment at which animals become sexually mature. If this theory was correct, then it might be that fat cells function as a time switch. If you have accumulated enough during childhood, at a certain point the manufacture of leptin exceeds a critical level and the alarm goes off, and puberty starts.

In his experiments Zeinoaldini used growing rats that received thirty percent less to eat than normal. As a result the rats’ fat layers grew less quickly and their leptin level was lower. ‘Normally rats reach puberty at an age of three to six weeks,’ says Zeinoaldini. ‘But the low-calorie diet delayed the onset of puberty by a week. We achieved the same effect in normally fed rats by giving them a substance that deactivated the leptin. The other way round, the slimmed down rats entered puberty at the normal time when they were given leptin.’From the experiments, however, it emerged that leptin was not the only factor involved. ‘Even in rats with a low leptin level sex hormone production does start,’ says Zeinoaldini. ‘It just takes longer.’

To build up a bigger picture of what goes on in prepubertal rats, the Iranian also examined another hormone that is produced in high concentrations in the early life phase of organisms: growth hormone. ‘When we started to look at what leptin does in combination with the growth hormone we discovered that they interact,’ explains the researchers. ‘But we were not able to understand exactly how this works.’

Giving growth hormone had a small influence on the time at which puberty started but was not a determining factor. The growth hormone did however lead to a dramatic increase in the rats’ leptin concentrations. ‘That little then happens is perhaps because the body becomes resistant to leptin,’ hypothesises Zeinoaldini. ‘But perhaps something totally different is happening. It is an interesting subject for further research.’ Zeinoaldini will not be doing that research himself; he is returning to Iran. / WK

Saeed Zeinoaldini will receive his PhD on 3 June. His promotor is Professor Daan van der Heide, chair of Human and Animal Physiology.

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