The decision of male medaka to mate or fight depends on two complementary androgen signaling pathways

Abstract

Adult male animals typically court and attempt to mate with females, while attacking other males. Emerging evidence from mice indicates that neurons expressing the estrogen receptor ESR1 in behaviorally relevant brain regions play a central role in mediating these mutually exclusive behavioral responses to conspecifics. However, the findings in mice are unlikely to apply to most other vertebrates, where androgens, rather than estrogens, have been implicated in male behaviors. Here we report that male medaka (Oryzias latipes) lacking one of the two androgen receptor subtypes (Ara) are less aggressive toward other males and instead actively court them, while those lacking the other subtype (Arb) are less motivated to mate with females and conversely attack them. These findings indicate that, in male medaka, the Ara- and Arb-mediated androgen signaling pathways facilitate appropriate behavioral responses, while simultaneously suppressing inappropriate responses, to males and females, respectively. Notably, males lacking either receptor retain the ability to discriminate the sex of conspecifics, suggesting a defect in the subsequent decision-making process to mate or fight. We further show that Ara and Arb are expressed in intermingled but largely distinct populations of neurons, and stimulate the expression of different behaviorally relevant genes including galanin and vasotocin, respectively. Collectively, our results demonstrate that male teleosts make adaptive decisions to mate or fight as a result of the activation of one of two complementary androgen signaling pathways, depending on the sex of the conspecific that they encounter.

Neuroestrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka

“…We then performed a similar analysis for the other AR subtype, Arb. Expression of arb was significantly lower in cyp19a1b −/− than in cyp19a1b +/+ males in other preoptic and hypothalamic nuclei activated upon mating and/or attack (15), including the PMp, aPPp, and NPT ( P = 0.0009, 0.0413, and 0.0021, respectively) (Fig. 2, H and I).…”

“…To test this hypothesis, we first examined ara expression in the brain of cyp19a1b -deficient males by in situ hybridization analysis. Expression of ara was significantly lower in cyp19a1b −/− males than in cyp19a1b +/+ males in several preoptic and hypothalamic nuclei that are activated upon mating and/or attack in males (15), including the PPa, pPPp, and NVT ( P = 0.0134, 0.0372, and 0.0008, respectively) (Fig. 2, F and G; see Table S1 for abbreviations of brain nuclei).…”

“…1C). The mating behavior of medaka follows a stereotypical pattern, wherein a series of followings, courtship displays, and wrappings by the male leads to spawning (15). Because 11KT, the primary driver of male-typical behaviors in teleosts, was increased in cyp19a1b -deficient males, we predicted that these fish would engage more actively in mating.…”

“…To ascertain whether cyp19a1b -deficient males are indeed less motivated to mate, we further tested their mating behavior using esr2b -deficient females, which are unreceptive to male courtship (10), as stimulus females (Fig. 1E); this test eliminates the influence of female receptivity, facilitating an exclusive evaluation of male motivation to mate with females (15). We found that cyp19a1b −/− males showed significantly longer latencies to initiate followings ( P = 0.0129 versus cyp19a1b +/+ , P = 0.0060 versus cyp19a1b +/− ), courtship displays ( P = 0.0003 versus cyp19a1b +/+ , P = 0.0006 versus cyp19a1b +/− ), and wrapping attempts ( P = 0.0009 versus cyp19a1b +/+ , P = 0.0282 versus cyp19a1b +/− ) (Fig.…”

“…We considered that the impaired male-typical behaviors of cyp19a1b -deficient males might be reasonably attributed to either reduced E2 or increased 11KT in the brain. The latter possibility seemed unlikely because 11KT/AR signaling strongly promotes male-typical behaviors in teleosts (15, 18); therefore, we tested the former possibility by examining whether E2 treatment would rescue the behavioral phenotypes of cyp19a1b -deficient males (Fig. 2A).…”