- SCIENCE NEWS This Week

terns. Some hormones, for example, cause the greatest effects at low and high doses, with little effect at intermediate exposures. This dose-response pattern, known as a U-shaped curve, has also been seen with hormonelike pollutants. Toxicologists are currently at a loss to explain it, says vom Saal.

Porter’s team speculates that their mouse results resemble the low end ofa U-shaped curve. They conjecture that small, but not large, concentrations of herbicides might interfere with hormones that control embryo implantation.

The researchers may be seeing a com- plicated mixture of responses by the body, says h a Soto of rifts University School of Medicine in Boston. “It’s counterintuitive, but that doesn’t mean the effect doesn’t exist,” she says.

W e don’t have the answers to how this works,” says vom Sad. However, he adds, toxicologists should redesign their stan- dard experiments. To estimate the envi- ronmental exposure that poses no risk, they should collect precise data on very low as well as high doses. -J. PICKRELL

Making Bone Novel form of vitamin D builds UD rat skeleton

Calcium is indispensable for bone growth, and vitamin D is needed to maintain proper amounts of calcium in the body. But as people age, they lose bone mass, often despite taking supplements of calcium and vitamin D.

Now, lab tests show that a newly syn- thesized form of vitamin D, called 2MD, induces bohe-making cells to capture cal- cium and fortify bone mass. When given to rats, 2MD significantly increases the animals’ bone density, researchers report in the Oct. 15 Proceedings of the National Academy of Sciences.

The findings appear so promising that study coauthor Hector F. DeLuca, a bio- chemist at the University of Wiscon- sin-Madison, is planning to seek regula- tory approval to test 2MD in people by the end of the year. The drug’s full name is 2-methylene-lg-nor-( 205)-la,25(OH),D3

DeLuca and his colleagues synthesized 2MD by tinkering with a part of the vita- min D molecule that binds to a molecu- lar receptor on the surface of cells. When

normal vitamin D locks onto this recep- tor, it acts like a hormone and orches- trates the release of other chemicals that balance blood concentrations of calcium and phosphates.

The researchers found that 2MD also binds to the vitamin D receptor-but with vastly different results. In lab-dish exper- iments with cells called osteoblasts, 2MD boosted the mineralization that’s normally part of bone manufacture to at least five times that of osteoblasts exposed to vitamin D, and to about 20 times that of osteoblasts not exposed to any form of the vitamin.

Next, DeLuca and his team gave 2MD to mature female rats whose ovaries had been removed. This animal model approxi- mates human menopause, in which women stop pro- ducing the bone-preserv- inn hormone estrogen.

chicks more robust, competitive, and therefore more likely to reproduce.

The new finding complicates other sci- entists’ notion that such an extra dose of hormone might make an egg turn out male instead of female.

Theories of parental favoritism rest on the idea that, in bad times-such as when a hen is near the bottom of the pecking

order-sons may not grow up to win the mating game. Then, investing in daughters is a safer bet because in many species, includ- ing chickens, low- ranked females are more likely to have off- spring than low-ranked males are. “If you’re a bad male, you don’t get any success,” says Muller. “But if you’re a

HEN’S CHOICE Topranklng leghorns dosed their sons with extra male hormones.

bad female, you still have matings.”

The study by Muller and his colleapues adds

The treated rats’ over21 bone density over 23 weeks grew by 9 percent, while similar rats not getting 2MD saw no improvement. In the 2MD-treated rats, vertebral bone density rose 25 percent, far more than the average.

The drug is given orally, and the studies have found no toxicity.

It appears that 2MD “is an extremely potent molecule,” says biochemist Glenville Jones of Queen’s University in Kingston, Ontario. He notes that the Japanese company Chugai Pharmaceuti- cals in Tokyo has developed a drug called ED-71-another vitamin D analog-that also shows promise in spurring osteoblasts to form bone. -N. SEPPA

Chicken Rank Hen social position shifts egg hormones - A study of leghorn chickens has linked hormone concentrations in a hen’s eggs to her rank in the pecking order.

The yolks of low-ranking hens’ eggs harboring males have about the same con- centrations of testosterone and one of its chemical precursors as do yolks of eggs containing female embryos, says Wendt Muller of the University of Groningen in the Netherlands. The male-to-be eggs of top females, however, have an extra dose of these hormones, Muller and his col- leagues report in an upcoming Proceed- ings of the Royalsociety ofLondon B. The researchers speculate that parental invest- ment of extra male hormones may make

- to a growing body of evidence supporting shifts in maternal favoritism. Some females even adjust the ratio of male to female off- spring depending on the circumstances.

Just what biochemical mechanism might be behind such shifts has been quite a puzzle. Scientists have considered hormones in the yolk, which is produced before the sex of the chick embryo is determined. A 1993 study hadn’t found differences in male hormones between yolks of male and female canary eggs. But Marion Petrie of the University of New- castle in Newcastle upon Tyne in England and her colleagues last year reported find- ing that the concentrations of four male hormones in the egg yolks of 10-day-old male peafowl embryos differed from those in yolks of females. Petrie’s study didn’t consider pecking order.

In their recent work, Muller and his colleagues checked testosterone and a hormone precursor, androstenedione, in 3-day-old eggs from five leghorn groups. When the researchers didn’t take into account the rank of the mothers, the two sexes didn’t show consistent differences in yolk hormones. However, when the inves- tigators examined only eggs from plump, high-ranking mothers, differences between the sexes appeared.

This result dashes any hopes scientists might have had that sex-ratio manipula- tion could be as straightforward as adding a dash of testosterone to the yolk to make males. “It’s not so simple,” Miiller concludes.

d There may not be a direct link between

egg sex and yolk hormones, but the Miiller g experiment can’t completely dismiss the p idea, says Petrie. -S. MlLlUS m

230 OCTOBER 1 2 , 2002 VOL. 162 SCIENCE NEWS