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Estrogen in the male brain
Sexual behavior is abolished in male mice without estrogen-receptor genes
Edward R. Winstead

Disrupting the estrogen-receptor genes causes an almost complete shutdown of sexual behavior in male mice. In a recent study, male mice without the estrogen-receptor genes 'ERa' and 'ERß' did not respond to highly receptive females, either by attempting to mate or by making the ultrasonic vocalization that normally accompanies 'sexual chasing' or pre-mating behavior. Disrupting the genes, however, had a somewhat different effect on male aggressive behavior, suggesting to the researchers that these two reproduction-related social behaviors require different contributions from estrogen-receptor genes.

Sonoko Ogawa, of The Rockefeller University in New York, led the study. "We are primarily interested in how estrogen works in the brain and how it regulates reproduction-related behavior," says Ogawa. She collaborates on research at Rockefeller with Professor Donald W. Pfaff, of the Laboratory of Neurobiology and Behavior. A paper describing the study appeared in Proceedings of the National Academy of Sciences.

Estrogen receptors are found in numerous sites in the brain, and the development in recent years of estrogen 'knockout' mice has made it possible to study the hormone's role in behavior. The field has progressed far enough, the authors write in their paper, that "we can attempt to move beyond the classical Beadle and Tatum 'one gene, one enzyme' formulation to discover patterns of gene activation influencing patterns of behavior." (For more on Beadle and Tatum see GNN's Genetics and Genomics Timeline)

The abolition of sexual function in males lacking both receptor genes surprised the researchers, says Ogawa. Her team previously investigated the effects of disrupting ERa or ERß on reproductive-related social behavior in male mice. In the current study, the researchers repeated those experiments using four types of male mice—ERa knockouts; ERß knockouts; double knockouts (no ERa or ERß); and males lacking the enzyme involved in synthesizing estrogen, aromatase.

The persistence of some sexual behavior, such as simple mounting, in animals with a single receptor gene suggests that there may be some redundancy in function of the ER genes, says a commentary that accompanies the study. "This appears to be the first example of such complementarity, but no doubt other examples will be reported in the future," write Evan R. Simpson and Susan R. Davis, of Prince Henry's Institute of Medical Research, in Victoria, Australia. "These results," they conclude, "point to an important role for estrogens in both male sexual behavior and male aggressive behavior."

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Ogawa, S. et al. Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta. Proc Natl Acad Sci U S A 97, 14737-14741 (Dec 19 2000).
Simpson, E. R. and Davis, S. R. Another role highlighted for estrogens in the male: Sexual behavior. Proc Natl Acad Sci U S A 97, 14038-14040 (Dec 19 2000).

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