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Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network. This network is directly implicated in the expression of a large range of social behaviors. The primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). An additional goal was to test the feasibility and effectiveness of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps using male sexual behavior as the aromatase dependent measure. We demonstrate that this mode of administration results in the strongest inhibition of both copulatory behavior and sexual motivation ever observed in this species, while other social behaviors were variably affected. Sexual motivation and the tendency to approach a group of conspecifics including females clearly seem to depend on brain aromatase, but the effects of central estrogen production on aggressive behavior and on the motivation to approach males remain less clear.

Estrogens play a key role in the sexual differentiation of the brain and behavior. While early estrogen actions exert masculinizing effects on the brain of male rodents, a diametrically opposite effect is observed in birds where estrogens demasculinize the brain of females. Yet, the two vertebrate classes express similar sex differences in the brain and behavior. Although ERα is thought to play a major role in these processes in rodents, the role of ERβ is still controversial. In birds, the identity of the estrogen receptor(s) underlying the demasculinization of the female brain remains unclear. The aim of the present study was thus to determine in Japanese quail the effects of specific agonists of ERα (propylpyrazole triol, PPT) and ERβ (diarylpropionitrile, DPN) administered at the beginning of the sensitive period (embryonic day 7, E7) on the sexual differentiation of male sexual behavior and on the density of vasotocin-immunoreactive (VT-ir) fibers, a known marker of the organizational action of estrogens on the quail brain. We demonstrate that estradiol benzoate and the ERβ agonist (DPN) demasculinize male sexual behavior and decrease the density of VT-ir fibers in the medial preoptic nucleus and the bed nucleus of the stria terminalis, while PPT has no effect on these measures. These results clearly indicate that ERβ, but not ERα, is involved in the estrogen-induced sexual differentiation of brain and sexual behavior in quail.

Male androphilia (i.e., male sexual attraction to other adult males) is known to cluster within families. Some studies demonstrate that male androphilia clusters in both the paternal and maternal familial lines, whereas other studies demonstrated that it clusters only in the latter. Most of these studies were conducted in Euro-American populations where fertility is low and the sexual orientation of male relatives can sometimes be difficult to ascertain. These two factors can potentially confound the results of such studies. To address these limitations, we examined the familial patterning of male androphilia among the Istmo Zapotec of Oaxaca, Mexico--a high fertility, non-Euro-American population where androphilic males are known locally as muxes, a third gender category. The Istmo Zapotec recognize two types of muxes--muxe gunaa and muxe nguiiu--who typify the transgender and cisgender forms of male androphilia, respectively. We compared the familial patterning of male androphilia between muxe gunaa and muxe nguiiu, as well as between gynephilic men and muxes (both cisgender and transgender forms combined). Istmo Zapotec muxe gunaa and muxe nguiiu exhibit similar familial patterning of male androphilia. Overall, muxes were characterized by significantly more muxe relatives than gynephilic men. This familial patterning was equivalent in both the paternal and maternal lines of muxes. The population prevalence rate of male androphilia was estimated to fall between 3.37-6.02% in the Istmo Zapotec. This is the first study that has compared cisgender and transgender androphilic males from the same high fertility population and demonstrated that the two do not differ with respect to the familial patterning of male androphilia.