BRIEF TREATMENT WITH AN AROMATASE INHIBITOR DURING SEX-DIFFERENTIATION CAUSES CHROMOSOMALLY FEMALE SALMON TO DEVELOP AS NORMAL, FUNCTIONAL MALES

Although many studies implicate sex steroids in the process of sexual differentiation, the exact role played by these substances in lower ve rtebrates, especially teleost fish, is not clear, since it is not conc lusively known whether sex steroids are the cause or an early conseque nce of sex differentiation. By hormonal manipulation and specific cros sings, it is possible to produce all-female stocks of the otherwise go nochoristic chinook salmon (Oncorhynchus tshawytscha). These all-femal e stocks are an excellent model to study the effects of steroids on se xual differentiation since the genetic sex is known before the actual differentiation of the embryonic gonads takes place. In the present st udy, we show that treatment with a nonsteroidal inhibitor of aromatase , the enzyme that catalyzes the conversion from androgens to estrogens , for only 2 hours when the gonads were bipotent, caused genetic femal es to develop into normal males. Furthermore, these males had testes w hich were indistinguishable both in size and in structure from those o f genetic males, and completed all the stages of spermatogenesis. At 2 years of age, these males produced viable sperm capable of inducing n ormal embryonic development when used to fertilize eggs, with a result ing all-female progeny. These results provide strong support for Yamam oto's theory (Yamamoto, '69) that androgens and estrogens are natural sex inducers in gonochoristic fish, and suggest that aromatase plays a pivotal role in the sex differentiation of salmon. Thus, by brief tre atment with an aromatase inhibitor at a specific time in development, an organism was induced to develop a functional, phenotypic sex differ ent from its genetic sex. (C) 1994 Wiley-Liss, Inc.