Pergamon J. Steroid Biochem. Molec. Biol. Vol. 53, No. 1-6, pp. 267-275, 1995 Copyright :( 1995 Elsevier Science Ltd 0960-0760(95)00064-X Printed in Great Britain. All rights reserved 0960-0760/95 $9.50 + 0.00 Sexual Differentiation of Brain and Behavior in Quail and Zebra Finches: Studies with a New Aromatase Inhibitor, R76713 A. Foidart and J. Balthazart* Laboratory of Biochemistry, University of Liege, 17 place Delcour (Bat. LI), B-4020 Liege, Belgium In many species of vertebrates, major sex differences affect reproductive behavior and endocrinology. Most of these differences do not result from a direct genomic action but develop following early exposure to a sexually differentiated endocrine milieu. In rodents, the female reproductive phenotype mostly develops in the absence of early steroid influence and male differentiation is imposed by the early action of testosterone, acting at least in part through its central conversion into estrogens or aromatization. This pattern of differentiation does not seem to be applicable to avian species. In Japanese quail (Coturnixjaponica), injection of estrogens into male embryos causes a permanent loss of the capacity to display male-type copulatory behavior when exposed to testosterone in adulthood. Based on this experimental result, it was proposed that the male reproductive phenotype is "neutral" in birds (i.e. develops in the absence of endocrine influence) and that endogenous estradiol secreted by the ovary of the female embryo is responsible for the physiological demasculinization of females. This model could be recently confirmed. Females indeed display a higher level of circulating estrogens that males during the second part of their embryonic life. In addition, treatment of female embryos with the potent aromatase inhibitor, R76713 or racemic vorozole TM which suppresses the endogenous secretion of estrogens maintains in females the capacity to display the full range of male copulatory behaviors. The brain mechanisms that control this sexually differentiated behavior have not been identified so far but recent data suggest that they should primarily concern a sub-population of aromatase-immunoreactive neurons located in the lateral parts of the sexually dimorphic preoptic nucleus. The zebra finch (Taeniopygia guttata) exhibits a more complex, still partly unexplained, differentiation pattern. In this species, early treatment with exogenous estrogens produces a masculinization of singing behavior in females and a demasculinization of copulatory behavior in males. Since normal untreated males sing and copulate, while females never show these behaviors even when treated with testosterone, it is difficult to understand under which endocrine conditions these behaviors differentiate. In an attempt to resolve this paradox, we recently treated young zebra finches with R76713 in order to inhibit their endogenous estrogens secretion during ontogeny and we subsequently tested their behavior in adulthood. As expected, the aromatase inhibitor decreased the singing frequency in treated males but it did not affect the male-type copulatory behavior in females nor in males. In addition, the sexuality differentiated brain song control nuclei which are also masculinized in females by early treatment with estrogens, were not affected in either sex by the aromatase inhibitor. In conclusion, available data clearly show that sexual differentiation of reproductive behaviors in birds follows a pattern that is almost opposite to that of mammals. This difference may be related to the different mechanisms of sex determination in the two taxa. In quail, the ontogeny of behavioral differentiation is now well understood but we only have a very crude notion of the brain structures that are concerned. By contrast, in zebra finches, the brain mechanisms controlling the sexually differentiated singing behavior in adulthood have been well identified but we do not understand how these structures become sexually dimorphic during ontogeny. J. Steroid Biochem. Molec. Biol., Vol. 53, No. 1-6, pp. 267-275, 1995 Proceedings of the IX International Congress on Hormonal Steroids, Dallas, Texas, U.S.A., 24-29 September 1994. *Correspondence to J. Balthazart. 267