A new breadth to estrogen's bisexuality.

Most people have been taught to think of estrogens as female sex hormones and androgens as male sex hormones. "But that's simply not true," notes Donald W. Pfaff.

Indeed, a pair of studies by Pfaff, a neurobiologist at Rockefeller University in New York, and his colleagues has unveiled estrogen's previously unrecognized depth and breadth in establishing gender-specific behaviors in both males and females.

Estrogen and other hormones operate by binding to receptors on or in cells and triggering the production of one or more chemical products. Pfaff's team worked with mutant mice born without the normal receptors for estrogen. These males, which don't respond to estrogen, had trouble mating in adulthood. Their reproductive organs "looked all right," Pfaff notes. Moreover, the animals tried to mate, he says, "so their motivation was not affected." What had been compromised was their ability to penetrate the female and release sperm, suggesting that their problems trace to some neurobiological defect, Pfaff says.

This wasn't their only behavioral peculiarity, observes coauthor Sonoko Ogawa, a behavioral neuroscientist at Rockefeller. The mutant males proved far less aggressive and exhibited less stereotypical masculine social behavior than their male littermates, which responded normally to the presence of estrogen. The team reports its findings in the Feb. 18 Proceedings of the National Academy of Sciences.

In the December 1996 Neuroendocrinology, the same team reported a suite of comparably atypical behaviors in female mice possessing the same genetic inability to respond to estrogen. Not only did they eschew the pup-nurturing behavior characteristic of females-and evident in normal littermates-they also exhibited the territorial aggression toward males usually seen only in males. In fact, Pfaff says, "a donnybrook ensued" whenever one of these mutant females was introduced to a normal male.

Clearly, Pfaff concludes, estrogen appears to be "a basic contributor to normal sexuality in both genders."

The sexual behavior of the estrogen-insensitive males is "very similar to what Earl Gray, in our lab, reported in rats prenatally exposed to dioxin," notes toxicologist Linda S. Birnbaum of the Environmental Protection Agency in Research Triangle Park, N.C. Gray found "that the little boys get just as excited [as normal rats] but then have a heck of a time doing it-and they've got real bad aim," Birnbaum observes (SN: 7/15/95, p. 44).

Pharmacologist Richard E. Peterson of the University of Wisconsin-Madison also has seen similar effects in rats exposed to dioxin (SN: 5/30/92, p. 359). He now predicts that the data from these studies with estrogen-insensitive rodents will open up new areas of research on the behavioral effects of weak estrogen mimics-pollutants that may block the far more potent estrogen's access to its receptor during critical periods of development.