Researchers tapping into the estrogen pathway that regulates fertility in males have found two independent roles of the hormone, and they may have uncovered a new approach for developing a male contraceptive. In a paper that appeared in the Nov. 20 issue of the Proceedings of the National Academy of Science, University of Illinois scientists report that estrogen regulates fluid reabsorption in the male reproductive tract by triggering a protein involved in sodium transport. They also describe how estrogen sustains the morphological architecture of the efferent ductules.
"We were not expecting this second role of estrogen," said Rex A. Hess, a professor of reproductive biology and toxicology at the University of Illinois College of Veterinary Medicine. "This structure-sustaining role appears to be independent of estrogen's molecular function of regulating ion transport. This tells us that estrogen is important for the expression of other genes with distinct physiological and morphological functions."
Hess and colleagues had documented in 1997 that estrogen was vital for fluid reabsorption during the transfer of sperm in fluid from the testis through the efferent ductules to the epididymis, where sperm matures and is stored. The PNAS paper provides a molecular picture of what estrogen does.
Efferent ductules are small tubes that produce concentrated semen. In a series of experiments using mice lacking the estrogen receptor or proteins thought to be regulated by estrogen, the scientists showed that when sodium transport did not occur, excess fluid diluted the sperm, leaving mice infertile. However, when estrogen receptor was present, epithelial cells were normal in appearance, even when sodium transport was abolished in the mice lacking the protein NHE3.
Hess and colleagues discovered that NHE3, which is responsible for the transport of sodium into and out of cells, was directly responsible for luminal fluid reabsorption under estrogen regulation. "Thus, blockage of the estrogen receptor could provide a new target for developing the perfect contraceptive in the male," Hess said.
"When we treated animals with a potent anti-estrogen compound, we saw a decline of messenger RNA necessary for sodium transport," said Qing Zhou, a doctoral researcher working with Hess.
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