Rapid effects of estradiol on male aggression depend on photoperiod in reproductively non-responsive mice (original) (raw)
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Nongenomic effects of estradiol on aggression under short day photoperiods
Hormones and Behavior, 2013
In several vertebrate species, the effects of estrogens on male aggressive behavior can be modulated by environmental cues. In song sparrows and rodents, estrogens modulate aggression in the nonbreeding season or winter-like short days, respectively. The behavioral effects of estrogens are rapid, which generally is considered indicative of nongenomic processes. The current study further examined the hypothesis that estradiol acts nongenomically under short days by utilizing a protein synthesis inhibitor, cycloheximide (CX). Mice were housed in either short or long day photoperiods, and treated with an aromatase inhibitor. One hour before resident-intruder testing mice were injected with either CX or saline vehicle, and 30 min later were treated orally with either cyclodextrin conjugated estradiol or vehicle. Under short days, mice treated with estradiol showed a rapid decrease in aggressive behavior, independent of CX administration. CX alone had no effect on aggression. These results show that protein synthesis is not required for the rapid effects of estradiol on aggression, strongly suggesting that these effects are mediated by nongenomic processes. We also showed that estradiol suppressed c-fos immunoreactivity in the caudal bed nucleus of the stria terminalis under short days. No effects of estradiol on behavior or c-fos expression were observed in mice housed under long days. Previously we had also demonstrated that cage bedding influenced the directional effects of estrogens on aggression. Here, we show that the phenomenon of rapid action of estradiol on aggression under short days is a robust result that generalizes to different bedding conditions.
Hormones and Behavior, 2008
Testosterone or its metabolite, estrogen, regulates aggression in males of many mammalian species. Because plasma testosterone levels are typically positively correlated with both aggression and reproduction, aggression is expected to be higher when males are in reproductive condition. However, in some photoperiodic species such as Siberian hamsters (Phodopus sungorus), males are significantly more aggressive in short day lengths when the testes are regressed and circulating testosterone concentrations are reduced. These results led to the formation of the hypothesis that aggression is modulated independently of circulating steroids in Siberian hamsters. Thus, recent studies have been designed to characterize the role of other neuroendocrine factors in modulating aggression. However, aggression may be mediated by testosterone or estrogen despite basal concentrations of these steroids by increasing sensitivity to steroids in specific brain regions. Consistent with this hypothesis, we found that males housed under short days have increased expression of estrogen receptor α in the bed nucleus of the stria terminalis, medial amygdala, and central amygdala. Neural activation in response to an aggressive encounter was also examined across photoperiod.
Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways
Proceedings of The National Academy of Sciences, 2007
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.
Effects of photoperiod and experience on aggressive behavior in female California mice
Behavioural Brain Research, 2010
Aggressive behavior among females is observed in many species, but the mechanisms of this behavior have historically been understudied. In many species of rodents, winter-like short day photoperiods induce increased aggression levels compared to summer-like long day photoperiods. Recent reports in hamsters show that short days also increase aggression in females. We examined the effects of photoperiod on aggression in female California mice, and for the first time compare brain activity of aggression-tested female rodents under different photoperiods. We observed that female California mice were more aggressive when housed in short days versus long days. Intriguingly, we also observed that under long days female attack latency decreases with repeated testing in resident intruder tests. These data suggest that winner effects that have been described in males may also occur in females. We also used the expression of phosphorylated extracellular signal-regulated kinases (pERK) in the brain to estimate brain activity during aggression tests. pERK can alter neuronal activity in the short term and in the long term can act as a transcription factor. Using immunoblot analyses we observed that aggression-induced pERK expression in the female bed nucleus of the stria terminalis (BNST) and medial amygdala occurs under both long and short days. Thus, the mechanisms controlling increased aggression under short days are still unclear and additional study is needed.
Neuroendocrine mechanisms of seasonal aggression in females
Gonadal hormones are key regulators of behavior through their actions on the central nervous system (CNS). To date, studies of aggression have overwhelmingly focused on actions of the gonadal hormone testosterone in the CNS. This ‘central’ dogma has resulted in an oversimplified framework of the neuroendocrine mechanisms underlying aggression. Evidence across taxa and sexes, however, demonstrates the lack of a consistent relationship between gonadal steroids and aggression, suggesting alternative, non-gonadal mechanisms that regulate this behavior. In order to fill this knowledge gap, I examined extra-gonadal neuroendocrine mechanisms regulating aggression in a year-round highly territorial mammal, Siberian hamsters. Within this seasonal context, I manipulated ambient day length (photoperiod) and melatonin, the biochemical signal of day length, to induce variation in reproductive phenotype and behavior. Hamsters responded to both photoperiod and melatonin by altering reproductive competence and displaying concomitant changes in behavior. Specifically, short-day females displayed increased aggression despite non-functional gonads and relatively low levels of the gonadal estrogen, estradiol, compared with long-day animals that displayed low aggression despite functional gonads. In this dissertation, I first examined how reproductive phenotype influences underlying variation in behavior across seasonal transitions and provide evidence for changes in estrogen-mediated mechanisms. Next, I manipulated temporal patterns of melatonin to show that females differentially alter aggression and modes of steroid metabolic conversion. Further, I illustrate bi-directional actions of adrenal steroids and behavior in a season-dependent manner. Finally, I propose an alternative mechanism in which the adrenal androgen, dehydroepiandrosterone (DHEA), serves as a key peripheral regulator of aggression and that melatonin coordinates a ‘seasonal switch’ from gonadal to adrenal regulation of aggression by direct action on adrenal glands. Using a whole-organism approach to probe the interconnectivity of target tissues, I show that aggression is differentially regulated across seasons, and highlight that DHEA serves a critical, but underappreciated role in the regulation of behavior. By examining the interactions of physiology and behavior across ecological contexts and time, these data expand the existing framework of the neuroendocrine regulation of social behavior and have broad applications to the evolution of behavior by highlighting key endocrine players natural selection could act upon.
Hormones and Behavior, 2000
Many nontropical rodent species display seasonal changes in both physiology and behavior that occur primarily in response to changes in photoperiod. Shortday reductions in reproduction are due, in part, to reductions in gonadal steroid hormones. In addition, gonadal steroids, primarily testosterone (T), have been implicated in aggression in many mammalian species. Some species, however, display increased aggression in short days despite basal circulating concentrations of T. The goal of the present studies was to test the effects of photoperiod on aggression in male Siberian hamsters (Phodopus sungorus) and to determine the role of T in mediating photoperiodic changes in aggression. In Experiment 1, hamsters were housed in long and short days for either 10 or 20 weeks and aggression was determined using a resident-intruder model. Hamsters housed in short days for 10 weeks underwent gonadal regression and displayed increased aggression compared to long-day-housed animals. Prolonged maintenance in short days (i.e., 20 weeks), however, led to gonadal recrudescence and reduced aggression. In Experiment 2, hamsters were housed in long and short days for 10 weeks. Half of the short-day-housed animals were implanted with capsules containing T whereas the remaining animals received empty capsules. In addition, half of the long-day-housed animals were castrated whereas the remaining animals received sham surgeries. Short-day control hamsters displayed increased aggression compared to either castrated or intact longday-housed animals. Short-day-housed T treated hamsters, however, did not differ in aggression from long-day-housed animals. Collectively, these results confirm previous findings of increased aggression in short-day-housed hamsters and suggest that short-dayinduced increases in aggression are inversely related to gonadal steroid hormones.
Rapid Effects of Estradiol on Aggression in Birds and Mice: The Fast and the Furious: Fig. 1
Integrative and Comparative Biology, 2015
Synopsis Across invertebrates and vertebrates, steroids are potent signaling molecules that affect nearly every cell in the organism, including cells of the nervous system. Historically, researchers have focused on the genomic (or ''nuclearinitiated'') effects of steroids. However, all classes of steroids also have rapid non-genomic (or ''membrane-initiated'') effects, although there is far less basic knowledge of these non-genomic effects. In particular, steroids synthesized in the brain (''neurosteroids'') have genomic and non-genomic effects on behavior. Here, we review evidence that estradiol has rapid effects on aggression, an important social behavior, and on intracellular signaling cascades in relevant regions of the brain. In particular, we focus on studies of song sparrows (Melospiza melodia) and Peromyscus mice, in which estradiol has rapid behavioral effects under short photoperiods only. Furthermore, in captive Peromyscus, estrogenic compounds (THF-diols) in corncob bedding profoundly alter the rapid effects of estradiol. Environmental factors in the laboratory, such as photoperiod, diet, and bedding, are critical variables to consider in experimental design. These studies are consistent with the hypothesis that locally-produced steroids are more likely than systemic steroids to act via nongenomic mechanisms. Furthermore, these studies illustrate the dynamic balance between genomic and non-genomic signaling for estradiol, which is likely to be relevant for other steroids, behaviors, and species.
Hormones and Behavior, 2001
Testosterone (T) mediates a trade-off, or negative correlation, between paternal behavior and aggression in several seasonally breeding avian species. However, the presence or absence of a T-mediated trade-off in mammals has received less attention. We examined the relationship between paternal behavior and territorial aggression in the biparental California mouse, Peromyscus californicus. In contrast to seasonally breeding birds, T maintains paternal behavior in this year-round territorial species. Castration reduced paternal behavior, whereas T replacement maintained high levels of paternal behavior. We hypothesize that T is aromatized in the brain to estradiol, which in turn stimulates paternal behavior. In contrast to paternal behavior, aggressive behavior was not reduced by castration. Interestingly, only sham males showed an increase in aggression across three aggression tests, while no change was detected in castrated or T-replacement males. Overall, trade-offs between aggression and paternal behavior do not appear to occur in this species. Measures of paternal behavior and aggression in a correlational experiment were actually positively correlated. Our data suggest that it may be worth reexamining the role that T plays in regulating mammalian paternal behavior.
2014
Violence is a serious public health problem and has a high impact on the quality of life of individuals across societies. Evolutionary, genetic, environmental, and cultural factors are closely interconnected as morbid causes. Animal models can be an important tool in the study of aggression. Regrouped Swiss Webster mice were selected based on mobility profile (Hypo, Normal; Hyper), which was defined by the tail suspension test. Our results demonstrate that Hyper mice (anxiety-like behavior) were more aggressive and violent than the other two categories, indicated by a pattern of aggressive behavior with a score 4+ in relation to score 1+ of Normal category. Hyper group, showed a decrease in total testosterone levels (-32.5% in relation to Norm group) and an increase in progesterone levels (+57.6% compared with the Norm group). We also observed a decrease in the weight of the testicles, the seminiferous tubules, Leydig and diploid spermatogenic cells number in hyper aggressive animal...
Hormones and Behavior, 2007
Among the suite of adaptations displayed by seasonally-breeding rodents, individuals of most species display reproductive regression and concomitant decreases in gonadal steroids during the winter. In addition, some species display increased aggression in short "winter-like" days compared with long "summer-like" day lengths. For example, male Syrian and Siberian hamsters held in short days express heightened levels of aggression that are independent of gonadal steroids. Virtually nothing is known, however, regarding seasonal aggression in female Siberian hamsters (Phodopus sungorus). Studies were undertaken to determine female levels of aggression in long and short days as well as the role of gonadal steroids in mediating this behavior. In Experiment 1, females were housed in long or short days for 10 weeks and resident-intruder aggression was assessed. Prior to testing, estrous cycle stages were determined by vaginal cytology and females were tested during both Diestrus I and Proestrus. In Experiment 2, hormone levels were experimentally manipulated; long-day females were ovariectomized (OVx) or given sham surgeries whereas short-day females were implanted with capsules containing 17β-estradiol (E 2 ) or Progesterone (P). In Experiment 3, both longand short-day females were ovariectomized and implanted with either an exogenous E 2 or blank capsule, or given a sham surgery. Short-day hamsters displayed increased aggression relative to long-day females. Aggression was not affected by estrous stage. There was no difference in aggression between long-day OVx and sham animals. Furthermore, neither exogenous E 2 nor P had any significant effect on aggression. These results support previous findings of increased non-breeding aggression and suggest that short-day aggression is not likely mediated by circulating levels of gonadal steroids. These results also suggest that the endocrine regulation of seasonal aggression may be similar between the sexes.