The first clue of a link between leptin and bone came from the observation that obese people, who tend to be less sensitive to leptin, have strong bones. Studies by geneticist Gerard Karsenty at Baylor College of Medicine in Houston confirmed the connection in mice, showing that leptin-deficient mice build up their bones as well as their body weight (ScienceNOW, 18 January, 2000). But just how the hormone delivered its message remained mysterious.

Now Karsenty's team reports in the 1 November issue of Cell that the nervous system plays a key role. The researchers joined the circulatory systems of two leptin-less mice and infused leptin into the brain of one. Bone cells responded only in the mouse that got the leptin, a result implicating the nervous system rather than a blood-borne message carrier. Leptin appears to act through the sympathetic nervous system: The bones of mice lacking norepinephrine--the signature neurotransmitter of the sympathetic system--didn't respond to leptin treatment, the team found. Finally, mice treated with beta blockers maintained normal bone mass even with their ovaries removed. This condition normally spurs bone loss, therefore raising the possibility that the drugs might combat osteoporosis.

"It's elegant science," says immunologist Steven Teitelbaum of Washington University in St. Louis. The work creates a "whole new vision of how bone cells are regulated." However, Teitelbaum cautions, whether the findings in mice will apply to humans is still open to question. If the results generalize, adds Gideon Rodan, a bone cell biologist at the Merck Research Laboratories in West Point, Pennsylvania, it might be possible to develop beta blockers that build bone strength without unwanted effects on blood pressure.

--KENDALL MORGAN