New chapters in the leptin tale.

The leptin story continues to unfold swiftly. In December 1994, investigators discovered that fat cells secrete this novel hormone and that it appears to travel to the brain and help regulate body weight. Last December, researchers reported that they had found a gene for a leptin receptor, a cell surface protein that recognizes the hormone and signals its presence to the rest of the cell (SN: 1/6/96, p. 6). Yet this receptor appeared to be absent in some brain regions long implicated in the regulation of weight. The leptin receptor was not detected, for example, in the hypothalamus.

Now, in a trio of papers appearing in the Feb. 9 Cell, the Feb. 15 Nature, and the Feb. 16 Science, scientists report that the receptor gene actually encodes a variety of leptin receptors, each of which has a different distribution in the brain. One version appears on hypothalamus cells. Furthermore, the investigators found that two obese strains of rodents owe their size to mutations in the leptin receptor gene.

The hormone also appears to play a role in reproduction, report researchers at the University of California, San Francisco (UCSF), in the March Nature Genetics. Leptin's discovery in 1994 resulted from the study of an obese strain of mice that fail to make the hormone because their leptin gene is mutated. Curiously, the female mice in this strain are infertile; hormonal abnormalities prevent them from ovulating.

Injections of leptin enable such females to ovulate, become pregnant, and bear healthy progeny, the investigators now report. In the brain, leptin probably controls the release of other reproductive hormones, but it may also act directly upon leptin receptors that researchers have recently found on ovaries. "The central question is what that receptor is doing in the ovary," says UCSF's Farid F. Chehab.

Chehab notes that women with very little body fat, such as marathon runners, sometimes stop menstruating. "They may be depleting their levels of leptin. And if you go below a certain threshold, reproduction shuts off," he says.