"Female" Hormone Critical for Male Reproduction

Estrogen is known as the "female hormone," but a study in tomorrow's issue of Nature suggests that it's not so fussy about gender. Researchers showed one way in which estrogen is critical to male reproduction in mice, and they suspect other roles for estrogen may soon be discovered.

For decades, scientists have known that estrogen and estrogen receptors are found in males, and over the last several years, clues to their function have emerged. A few male patients with estrogen and estrogen-receptor deficiencies showed bone growth abnormalities, and last year male estrogen-receptor knockout (ERKO) mice, which lack the gene for the receptor, were found to be infertile.

Physiologist and toxicologist Rex Hess of the University of Illinois, Champaign-Urbana, already suspected estrogen was important in male reproduction, partly because of the extremely high concentration of estrogen receptors in the efferent ductules--microscopic tubes that lead young sperm from the testis to the epididymis, where they mature. The ductules act as more than just pipes: They absorb fluid, concentrating the sperm during their trip, which improves their survival and the animal's sperm count. In their Nature paper, Hess and his colleagues at Illinois, the University of Missouri, Columbia, and the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, looked at the behavior of the ductules in ERKO mice.

Previous studies had shown that the ductules in these mice malfunction, but Hess and his colleagues provided a detailed description of what goes wrong. As the mice mature, the tube walls become swollen with fluid, eventually blocking the ductules and shutting down sperm production. When the team extracted ERKO ductules, filled them with fluid, and closed them off at each end, the ductules were unable to remove the fluid they contained and actually swelled by 46% in 24 hours. Controls shrunk in cross-sectional area by 82%. Normal ductules treated with an estrogen-blocking compound shrunk only 14%, suggesting that the dysfunction of the ERKO ductules is caused at least in part by their inability to bind estrogen.

"It's the first demonstration of something that estrogens actually do in the male, in the reproductive system," says Richard Sharpe of the U.K. Medical Research Council's Reproductive Biology Unit in Edinburgh. He notes that there is evidence of estrogen action throughout the male reproductive system, and it is possible that environmental toxins that mimic estrogen could interfere with any of estrogen's sites of action. Hess's results "open a new door" onto such questions, he says.