SEXUAL-DIFFERENTIATION OF BRAIN AND BEHAVIOR IN QUAIL AND ZEBRA FINCHES - STUDIES WITH A NEW AROMATASE INHIBITOR, R76713

In many species of vertebrates, major sex differences affect reproduct ive behavior and endocrinology. Most of these differences do not resul t from a direct genomic action but develop following early exposure to a sexually differentiated endocrine milieu. In rodents, the female re productive phenotype mostly develops in the absence of early steroid i nfluence and male differentiation is imposed by the early action of te stosterone, acting at least in part through its central conversion int o estrogens or aromatization. This pattern of differentiation does not seem to be applicable to avian species. In Japanese quail (Coturnix j aponica), injection of estrogens into male embryos causes a permanent loss of the capacity to display male-type copulatory behavior when exp osed 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 res ponsible for the physiological demasculinization of females. This mode l could be recently confirmed. Females indeed display a higher level o f circulating estrogens that males during the second part of their emb ryonic life. In addition, treatment of female embryos with the potent aromatase inhibitor, R76713 or racemic vorozole(TM) which suppresses t he endogenous secretion of estrogens maintains in females the capacity to display the full range of male copulatory behaviors. The brain mec hanisms that control this sexually differentiated behavior have not be en identified so far but recent data suggest that they should primaril y 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 partl y unexplained, differentiation pattern. In this species, early treatme nt with exogenous estrogens produces a masculinization of singing beha vior in females and a demasculinization of copulatory behavior in male s. Since normal untreated males sing and copulate, while females never show these behaviors even when treated with testosterone, it is diffi cult to understand under which endocrine conditions these behaviors di fferentiate. In an attempt to resolve this paradox, we recently treate d 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 sex uality differentiated brain song control nuclei which are also masculi nized in females by early treatment with estrogens, were not affected in either sex by the aromatase inhibitor. In conclusion, available dat a clearly show that sexual differentiation of reproductive behaviors i n birds follows a pattern that is almost opposite to that of mammals. This difference may be related to the different mechanisms of sex dete rmination in the two taxa. In quail, the ontogeny of behavioral differ entiation is now well understood but we only have a very crude notion of the brain structures that are concerned. By contrast, in zebra finc hes, the brain mechanisms controlling the sexually differentiated sing ing behavior in adulthood have been well identified but we do not unde rstand how these structures become sexually dimorphic during ontogeny.