In numerous vertebrate species including Japanese quail ( C e turnix coturnix japonica), actions of testosterone (T) on neuroendocrine target tissues are mediated in part by conversion to estrogenic and androgenic metabolites. In order to assess which pathways were favored in each identified androgen target area in quail brain and whether there were discernible sex differences, we developed a n assay for simultaneously quantifying aromatase, 5a-, and 50-reductase. In addition, we made the first definitive identification of aromatase in quail pituitary and compared all three enzyme activities in the pituitary of males and females. Enzymes were measured in tissue homogenates by the conversion of [3H]androstenedione to ["Hlestrone, [3H]5a-androstanedione, and 56-androstanedione. Aromatase activity was restricted to limbic tissues (anterior hypothalamus > posterior hypothalamus > septum > archistriatum containing nucleus taenia) while hyperstriatum, cerebellum, and midbrain containing nucleus intercollicularis were aromatase-negative. Quail pituitary aromatized androgen at rates equivalent to anterior hypothalamus1 pre-optic area (aHPOA). 5a-and 56-reductase were present in all tissues tested. Aromatase was significantly higher in aHPOA and pituitary of males, whereas 5a-reductase was significantly higher in female pituitary. These data suggest that a complex of androgen-metabolizing enzymes controls the neuroanatomic (spatial) distribution of active hormone in neuroendocrine tissues and that quantitative differences between males and females may account for sex differences in behavior.
For the full expression of testosterone (T) action in brain, as in peripheral target tissues, circulating hormone is transformed in situ to one or more biologically active metabolites (Martini, '82; Callard, '84; Hutchison and Steimer, '84). Three major irreversible androgen-metabolizing pathways have been identified in brain. Aromatization and 5areduction lead to synthesis of estradiol-17P and 5a-dihydrotestosterone (5a-DHT), respectively. Each of these metabolites binds to a separate receptor system and has unique actions on brain sex differentiation, sex behavior, and pituitary hormone secretion (for review, McEwen, '81). For example, in adult Japanese quail (Coturnix coturnix japonica), aromatization of androgens to estrogens appears to be essential for male copulatory behavior (Adkins et al., '80; Wada, '82), aggressiveness (Tsutsui and Ishii, %l), and locomotor activity (Wada, '82, '84), whereas testosterone per se and 5a-reduced androgens stimulate crowing and the strutting display (Adkins et al., '80; Balthazart et al., '84). The third pathway, 50-reduction, is presumed to be inactivating in that it leads to production of 50-DHT, which has no known receptor mechanism (Martini, '82) or demonstrated biological activity in brain or pituitary (Hutchison and Steimer, '84; Davies et al., '80). Nonetheless, since a variety of 56reduced steroids stimulate hematopoiesis in chick embryos CLevere et al., '67) and 50reduced steroids of the pregnane series have potent anesthetic properties (Holzbauer, '76), the exact biological role of 56 reduction remains unresolved.
Aromatase and 5a-reductase have been widely conserved through phylogeny, having Address reprint requests to Barney A. Schlinyer.