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Amanda Schaffer
FOR years, scientists thought they understood the skeleton. It serves as structural support for the body. It stores calcium and phosphate. It contributes to blood-cell development. And it serves, indispensably, as the creepy mascot of horror movies.
But as it turns out, there might be still more to bone.
A few years ago, researchers at Columbia University Medical Centre discovered, to everyone's surprise, that the skeleton seems to help regulate blood sugar. Now the team, led by a geneticist and endocrinologist at the university, Dr Gerard Karsenty, has found that bone might also play an unexpected role in reproduction. If the work pans out, it might help to explain some cases of low fertility in men.
''It's definitely an attention-grabber,'' says Dr William Crowley, of Harvard Medical School, who was not part of the research.
It is well known that the hormones oestrogen and testosterone, produced in the ovaries and testes, help to regulate bone growth. When women reach menopause, oestrogen levels decrease along with bone mass, putting them at increased risk of osteoporosis. As men age, their testosterone and oestrogen levels also decline. Men lose bone but much more slowly than women do. ''We thought that if the sex organs talk to the skeleton, then the skeleton should talk back to the sex organs,'' Karsenty says.
And, apparently, it does.
Early this year, Karsenty's team published a study demonstrating that in mice a protein called osteocalcin, which is produced by bone-forming cells called osteoblasts, binds to a specific receptor on cells of the testes. Male mice that were unable to make osteocalcin (due to genetic manipulation) produced less testosterone and were less fertile. When they mated, they had fewer and smaller offspring.
Fertility in female mice, on the other hand, was not affected by osteocalcin. Cells in their ovaries lacked the receptors to which the bone hormone binds. ''We were surprised by that,'' Karsenty says. ''We thought we'd find a hormone that regulated fertility in both sexes.'' Another compound, as yet unknown, might play the analogous role in females. Human testicular cells also have receptors for the hormone osteocalcin, Karsenty has found.
''I don't know of any hormone that functions in mice but not to some extent in humans,'' says a researcher at Maryland's Johns Hopkins University, Thomas Clemens. Still, the magnitude of the effect might not be the same as in mice.
The main hormone that stimulates testosterone production, in mice and men, is luteinizing, a protein made in the brain. Luteinizing hormone is ''the on-off switch'' for testosterone, Crowley says. Osteocalcin, on the other hand, looks more like a ''dimmer switch'' that modulates the process.
The question is, is it a critical mechanism or a back-up system? Does osteocalcin play a large role in problems such as low sperm count and low testosterone, or is it more peripheral?
Scientists now plan to study men with these problems and to measure their osteocalcin levels, Crowley says. Some of them might have a defect in osteocalcin that underlies their condition.
But, he says: ''I suspect this will turn out to be one chapter in an interesting and more complicated mystery.''
Karsenty has long argued that bone plays a central role in regulating body physiology. ''The body is not an assembly of silos that don't speak to each other but is full of surprising examples of crosstalk,'' he says.
In 2007, he showed that bone helps to regulate blood sugar, a result that startled hormone specialists. Working with mice, he reported that osteocalcin boosts insulin production in the pancreas and increases insulin sensitivity. Insulin, in turn, acts to lower blood sugar.
That work could prove relevant to diabetes, in which the body either does not produce enough insulin or stops heeding it.
Now, Karsenty hopes to unravel the complicated links binding the skeleton, sugar and gender. Bone mass tends to decline with age, he notes, as do blood-sugar control and fertility.
''One idea is that bone might not just be a victim of ageing. It might also be a contributor.''
The New York Times