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14 February 2005
Study Links Melatonin To Gonad Shrinkage
by George Atkinson

Melatonin is often used by shift workers and travelers who take the hormone to stave off drowsiness or jetlag, but Japanese and American researchers are suggesting that more caution should be exercised in its use. A new study, published in the Proceedings of the National Academy of Sciences, shows that melatonin, which is available without prescription, has broader effects in the brain than once thought. In experiments on birds, the researchers found that melatonin switches on a hormone called gonadotropin inhibitory hormone (GnIH), which has been found to have the opposite effect to the key hormone priming the body for sex - gonadotropin releasing hormone (GnRH). In the birds, switching off GnRH causes the gonads (testes) to shrink.

Although the role of melatonin is likely to be more complex in humans, the fact that the hormone has such a big effect on birds suggests it could have significant effects in humans, said University of California researcher George E. Bentley. "This is quite exciting in terms of potential effects of melatonin on the reproductive axis, that is, the link between the brain, the pituitary gland and the gonads," said Bentley. While melatonin could have beneficial effects, the current lack of knowledge of the hormone's function in the human brain troubles Bentley. "It really amazes me that melatonin is available in any pharmacy," he said. "It is a powerful hormone, and yet people don't realize that it's as 'powerful' as any steroid. I'm sure that many people who take it wouldn't take steroids so glibly. It could have a multitude of effects on the underlying physiology of an organism, but we know so little about how it interacts with other hormone systems."

Bentley became interested in melatonin's effects in the brain through his work with co-researcher Kazuyoshi Tsutsui on a new brain hormone, GnIH, that Tsutsui discovered in 2000. GnIH's discovery got a lot of attention at the time because it was one of the last remaining pieces of the brain's hormone system that controls reproduction. While most hormones produced by the brain have both agonists, often called "releasing hormones," to switch them on and antagonists to switch them off, GnRH was missing an antagonist. GnIH seemed to be that missing antagonist, and work by Tsutsui and Bentley confirmed its role in turning down production of GnRH and thus switching off the gonads. Though most of these studies were conducted on the Japanese quail or the white-crowned sparrow, a search of the human genome shows that humans have a gene for the same hormone. "This is a way in which puberty could be regulated, for example," Bentley said. "It adds a whole new dimension to reproductive biology, because there are a lot of clinical issues with reproduction and puberty".

To understand more about the role melatonin plays in the reproductive cycle of quail, the researchers raised male birds under different lighting conditions. Quail raised in simulated short days, which would be expected to produce high levels of melatonin in the brain, had correspondingly higher levels of GnIH than did quail raised with longer periods of light, which would be expected to produce less melatonin. In addition, the short-day males had larger testicles than the long-day males.

"There are a lot of unknowns in terms of potential effects of melatonin," Bentley concluded. "We know that GnIH affects the reproductive axis, but the GnIH neurons in the hypothalamus have fibers branching from them that transport the peptide around the brain to multiple brain areas - areas involved in basically every physiological and behavioral process you could imagine. So melatonin could affect a multitude of physiological systems via the GnIH system."

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