Fertility factor from the mouths of mice.

Fertility factor from the mouths of mice

Biology textbooks indicate that the hormones controlling the development of sperm come from two places--the testes themselves, and the pituitary and hypothalamus glands at the base of the brain. Researchers from the National Institutes of Health (NIH) have come up with a new locale, at least for mice--the submandibular gland, which lies beneath the tongue and in humans is what swells during mumps.

The submandibular gland produces a substance called epidermal growth factor (EGF), one of about a dozen known growth factors. While EGF stimulates growth of some cells in culture, until now its role in the body has been a mystery.

Osamu Tsutsumi, Hirohisa Kurachi and Takami Oka of NIH removed the submandibular glands of male mice. While the animals' testosterone levels did not fall and their behavior did not change, EGF dropped to unmeasurable levels and the number of mature sperm dropped to about half the level of mice that underwent "sham' operations, with their glands left intact. The researchers then injected the glandless mice with either EGF or another growth factor produced by the submandibular gland. Only EGF restored the sperm levels, they report in the Aug. 29 SCIENCE. EGF, they suggest, could be absorbed from the saliva into the blood via the digestive tract.

One reason for the long delay in determining EGF's action is that no known disease is marked by its absence, says Stanley Cohen of Vanderbilt University in Nashville, who discovered EGF about 30 years ago. Without a human model for what happens when EGF is not there, figuring out its function has been difficult. About the current work, Cohen says, "It is certainly interesting and warrants further experiments.'

If the work pans out, EGF will be the first known substance produced outside of the traditional reproductive organ-hypothalamus axis to have a vital, hormone-like function in reproduction. In previous research, the group found EGF also plays a role in female mice. Though present at only about one-tenth the concentration found in males, in female mice the factor is involved in the development of mammary glands as well as mammary tumors. The researchers also found that an antibody to EGF can halt the growth of the tumors.

Does a substance that cuts rodent sperm development without affecting testosterone levels, and stops the growth of breast tumors, have a potential role in humans as a contraceptive or cancer treatment? "It's going to be a long time before its usefulness in humans is known,' says Oka, "but it shows a way to approach the problems.'