Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways

Abstract

Despite recent discoveries of the specific contributions of genes to behavior, the molecular mechanisms mediating contributions of the environment are understudied. We demonstrate that the behavioral effects of estrogens on aggression are completely reversed by a discrete environmental signal, day length. Selective activation of either estrogen receptor ␣ or ␤ decreases aggression in long days and increases aggression in short days. In the bed nucleus of the stria terminalis, one of several nuclei in a neural circuit that controls aggression, estrogen-dependent gene expression is increased in long days but not in short days, suggesting that estrogens decrease aggression by driving estrogen-dependent gene expression. Estradiol injections increased aggression within 15 min in short days but not in long days, suggesting that estrogens increase aggression in short days primarily via nongenomic pathways. These data demonstrate that the environment can dictate how hormones affect a complex behavior by altering the molecular pathways targeted by steroid receptors.estrogen receptor ͉ social behavior ͉ Peromyscus polionotus ͉ seasonality G enes code for the molecular machinery that interacts with the environment to regulate behavior. Despite the importance of gene-environment interactions, relatively few studies have explored the mechanistic bases of these processes (1). These interactions may generate apparent inconsistencies in relationships between neurochemical systems and behavior (2). For example, in most birds and domesticated mice estrogens increase aggression, whereas estrogens decrease aggression or its components in Bluebanded gobies, California mice, and humans (3). This complexity in estrogenic modulation of aggression could be mediated by several factors including differential expression of estrogen receptor (ER) subtypes or differences in receptor activity after estrogen binding. In male vertebrates estrogens can be produced in the testes or synthesized in the brain from androgens. ERs can modulate physiology and behavior via both genomic and nongenomic pathways (4). Estrogens can alter the transcription of other genes by translocating to the nucleus and binding to estrogen response elements (ERE) or other response elements (5), a process mediated by an array of cofactors (6). Estrogens can also exert a variety of nongenomic effects that may be mediated by unique membrane-bound receptors (7) or the well characterized ER␣ (8) and ER␤ (9). Recent studies suggest ER␣ and ER␤ can be located at the membrane (10) and may facilitate phosphorylation of MAP kinase and CREB (11). Although the transduction of estrogenic signals has been studied intensively, comparatively little is known about how the environment affects estrogen action.Using a discrete environmental signal, day length (photoperiod), we have discovered a striking gene-environment interaction. Similar to other rodents, male beach mice (Peromyscus polionotus) exhibit testicular regression and are more aggressive when housed in winter-like short days (12...

Rapid enhancement of two-step wiring plasticity by estrogen and NMDA receptor activity

“…A substantial body of work demonstrates that the rapid actions of E2 affect cortically based cognitive function. Object recognition (13,14), reference memory (15), and aggression (26) have been shown to be influenced by acute E2 treatment. Furthermore, long-term potentiation and long-term depression in the forebrain are both enhanced by acute E2 administration (11,12).…”

Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats

“…exposure). Testosterone has its biological effects by binding to specific steroid receptors in target tissues (Simon and Lu, 2005;Trainor et al, 2007). Whether Seoul virus alters the density and distribution of androgen receptors, estrogen receptors, or both remains to be determined.…”

Rapid effects of estradiol on male aggression depend on photoperiod in reproductively non-responsive mice

“…Instead, it appears that photoperiod changes the molecular activity of estrogen receptors. Results from a microarray experiment showed that estrogen-dependent gene expression in the BNST was decreased in short days compared to long days (Trainor et al, 2007a). Furthermore, estradiol injections increased aggression within 15 min in male P. polionotus housed in short days, but had no effect on males housed in long days.…”

“…In Syrian hamsters (Mesocricetus auratus) (Garrett and Campbell, 1980;Jasnow et al, 2002;Caldwell and Albers, 2004), Siberian hamsters (Phodopus sungorus) (Jasnow et al, 2000;Demas et al, 2004;Wen et al, 2004), beach mice (Peromyscus polionotus) (Trainor et al, 2007a), and deer mice (Peromyscus maniculatus) (Trainor et al, 2007b), males are more aggressive in a resident-intruder test when tested in short days (8L: 16D) as opposed to long days (16L:8D). This effect has been considered paradoxical, because in each of these species housing in short days causes regression of testes and a corresponding decrease in testosterone (Jasnow et al, 2000(Jasnow et al, , 2002Trainor et al, 2006c).…”

“…The estrogen receptor hypothesis was tested with hormone manipulation experiments (Trainor et al, 2007a). In male P. polionotus, treatment with the aromatase inhibitor fadrozole increased aggression in long days but decreased aggression in short days.…”