This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
According to contemporary understanding, the only route to production of male reproductive structures, in humans and other mammals, involves the action of male hormones (androgens) during fetal life. In the absence of androgens, female reproductive structures develop. However, within this framework, female reproductive development is often neglected and characterized as a "default" condition. Female spotted hyenas are the most highly "masculinized" of all female mammals, with external reproductive structures that are, superficially, identical to those of the male. This experiment-of-nature provides an opportunity to challenge our understanding of reproductive development. If the hypothesis cited above is correct, the "masculine" reproductive anatomy of the female spotted hyena must have been produced by naturally circulating male hormones in a female mammal. Results to date suggest that, contrary to contemporary understanding, "masculinization" of the female spotted hyena is produced by an androgen-independent mechanism. Moreover, preliminary data indicate that traditional female hormones (i.e., estrogens) play a role in the normal development of external reproductive structures in both female and male hyenas, and in laboratory mice. During the tenure of this award we will systematically explore the interactions between estrogens and androgens that result in formation and development of external reproductive structures. This research will provide the first information on the role of estrogens on such development, and emphasize the active nature of reproductive development in all female mammals. Our prior research has been cited in the human medical literature, and our new results will have implications for understanding reproductive abnormalities in human beings. In addition, the existence of the hyena colony provides a valuable training resource for graduate students and postdoctoral fellows from U.C. Berkeley, and other universities in this country.
