Oestrogen regulates male aggression in the non-breeding season

Extensive research has focused on territorial aggression during the breeding season and the roles of circulating testosterone (T) and its conversion to 17beta-oestradiol (E2) in the brain. However, many species also defend territories in the non-breeding season, when circulating T-levels are low. The endocrine control of non-breeding territoriality is poorly understood. The male song sparrow of Washington State is highly territorial year-round, but plasma T is basal in the non-breeding season (autumn and winter). Castration has no effect on aggression in autumn, suggesting that autumnal territoriality is independent of gonadal hormones. However, non-gonadal sex steroids may regulate winter territoriality (e.g. oestrogen synthesis by brain aromatase). In this field experiment, we treated wild non-breeding male song sparrows with a specific aromatase inhibitor (fadrozole, FAD) using micro-osmotic pumps. FAD greatly reduced several aggressive behaviours. The effects of FAD were reversed by E2 replacement. Treatment did not affect body condition or plasma corticosterone, suggesting that all subjects were healthy These data indicate that E2 regulates male aggression in the non-breeding season and challenge the common belief that aggression in the non-breeding season is independent of sex steroids. More generally, these results raise fundamental questions about how sexual and/or aggressive behaviours are maintained in a variety of model vertebrate species despite low circulating levels of sex steroids or despite castration. Such non-classical endocrine mechanisms may be common among vertebrates and play an important role in the regulation of behaviour.     

Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows

Many studies have demonstrated that male aggression is regulated by testosterone. The conversion of testosterone to estradiol by brain aromatase is also known to regulate male aggression in the breeding season. Male song sparrows (Melospiza melodia morphna) are territorial not only in the breeding season, but also in the nonbreeding season, when plasma testosterone and estradiol levels are basal. Castration has no effect on nonbreeding aggression. In contrast, chronic (10 day) aromatase inhibitor (fadrozole) treatment decreases nonbreeding aggression, indicating a role for estrogens. Here, we show that acute (1 day) fadrozole treatment decreases nonbreeding territoriality, suggesting relatively rapid estrogen effects. In spring, fadrozole decreases brain aromatase activity, but acute and chronic fadrozole treatments do not significantly decrease aggression, although trends for some behaviors approach significance. In gonadally intact birds, fadrozole may be less effective at reducing aggression in the spring. This might occur because fadrozole causes a large increase in plasma testosterone in intact breeding males. Alternatively, estradiol may be more important for territoriality in winter than spring. We hypothesize that sex steroids regulate male aggression in spring and winter, but the endocrine mechanisms vary seasonally.     

Territorial aggression and hormones during the non-breeding season in a tropical bird

The hormonal control of territorial aggression in male and female vertebrates outside the breeding season is still unresolved. Most vertebrates have regressed gonads when not breeding and do not secrete high levels of sex steroids. However, recent studies implicate estrogens in the regulation of non-breeding territoriality in some bird species. One possible source of steroids during the non-breeding season could be the adrenal glands that are known to produce sex steroid precursors such as dehydroepiandrosterone (DHEA). We studied tropical, year-round territorial spotted antbirds (Hylophylax n. naevioides) and asked (1). whether both males and females are aggressive in the non-breeding season and (2). whether DHEA is detectable in the plasma at that time. We conducted simulated territorial intrusions (STIs) with live decoys to male and female free-living spotted antbirds in central Panama. Non-breeding males and females displayed robust aggressive responses to STIs, and responded more intensely to decoys of their own sex. In both sexes, plasma DHEA concentrations were detectable and higher than levels of testosterone (T) and 17beta-estradiol (E(2)). In males, plasma DHEA concentrations were positively correlated with STI duration. Next, we conducted STIs in captive non-breeding birds. Captive males and females displayed robust aggressive behavior. Plasma DHEA concentrations were detectable in both sexes, whereas T was non-detectable (E(2) was not measured). Plasma DHEA concentrations of males were positively correlated with aggressive vocalizations and appeared to increase with longer STI durations. We conclude that male and female spotted antbirds can produce DHEA during the non-breeding season and DHEA may serve as a precursor of sex steroids for the regulation of year-round territorial behavior in both sexes.     

Non-migratory stonechats show seasonal changes in the hormonal regulation of non-seasonal territorial aggression

In many birds and mammals, male territorial aggression is modulated by elevated circulating concentrations of the steroid hormone testosterone (T) during the breeding season. However, many species are territorial also during the non-breeding season, when plasma T levels are basal. The endocrine control of non-breeding territorial aggression differs considerably between species, and previous studies on wintering birds suggest differences between migratory and resident species. We investigated the endocrine modulation of territorial aggression during the breeding and non-breeding season in a resident population of European stonechats (Saxicola torquata rubicola). We recorded the aggressive response to a simulated territorial intrusion in spring and winter. Then, we compared the territorial aggression between seasons and in an experiment in which we blocked the androgenic and estrogenic action of T. We found no difference in the aggressive response between the breeding and the non-breeding season. However, similarly to what is found in migratory stonechats, the hormonal treatment decreased aggressive behaviors in resident males in the breeding season, whereas no effects were recorded in the non-breeding season. When we compared the aggressive responses of untreated birds with those obtained from migratory populations in a previous study, we found that territorial aggression of resident males was lower than that of migratory males during the breeding season. Our results show that in a resident population of stonechats T and/or its metabolites control territorial aggression in the breeding but not in the non-breeding season. In addition, our study supports the hypothesis that migratory status does modulate the intensity of aggressive behavior.     

Aggressive encounters differentially affect serum dehydroepiandrosterone and testosterone concentrations in male Siberian hamsters (Phodopus sungorus)

The gonadal hormone testosterone (T) regulates aggression across a wide range of vertebrate species. Recent evidence suggests that the adrenal prohormone dehydroepiandrosterone (DHEA) may also play an important role in regulating aggression. DHEA can be converted into active sex steroids, such as T and estradiol (E₂), within the brain. Previous studies show that circulating DHEA levels display diurnal rhythms and that melatonin increases adrenal DHEA secretion in vitro. Here we examined serum DHEA and T levels in long-day housed Siberian hamsters (Phodopus sungorus), a nocturnal species in which melatonin treatment increases aggression. In Experiment 1, serum DHEA and T levels were measured in adult male hamsters during the day (1200 h, noon) and night (2400 h, midnight). In Experiment 2, aggression was elicited using 5-min resident–intruder trials during the day (1800 h) and night (2000 h) (lights-off at 2000 h). Serum DHEA and T levels were measured 24 h before and immediately after aggressive encounters. In Experiment 1, there was no significant difference in serum DHEA or T levels between noon and midnight, although DHEA levels showed a trend to be lower at midnight. In Experiment 2, territorial aggression was greater during the night than the day. Moreover, at night, aggressive interactions rapidly decreased serum DHEA levels but increased serum T levels. In contrast, aggressive interactions during the day did not affect serum DHEA or T levels. These data suggest that nocturnal aggressive encounters rapidly increase conversion of DHEA to T and that melatonin may play a permissive role in this process.     

Dehydroepiandrosterone (DHEA) increases territorial song and the size of an associated brain region in a male songbird

In many species, male territorial aggression is tightly coupled with gonadal secretion of testosterone (T). In contrast, in song sparrows (Melospiza melodia morphna), males are highly aggressive during the breeding (spring) and nonbreeding (autumn and early winter) seasons, but not during molt (late summer). In aggressive nonbreeding song sparrows, plasma T levels are basal (< or = 0.10 ng/ml), and castration has no effect on aggression. However, aromatase inhibitors reduce nonbreeding aggression, indicating a role for estrogen in wintering males. In the nonbreeding season, the substrate for brain aromatase is unclear, because plasma T and androstenedione levels are basal. Aromatizable androgen may be derived from plasma dehydroepiandrosterone (DHEA), an androgen precursor. DHEA circulates at elevated levels in wintering males (approximately 0.8 ng/ml) and might be locally converted to T in the brain. Moreover, plasma DHEA is reduced during molt, as is aggression. Here, we experimentally increased DHEA in wild nonbreeding male song sparrows and examined territorial behaviors (e.g., singing) and discrete neural regions controlling the production of song. A physiological dose of DHEA for 15 days increased singing in response to simulated territorial intrusions. In addition, DHEA treatment increased the volume of a telencephalic brain region (the HVc) controlling song, indicating that DHEA can have large-scale neuroanatomical effects in adult animals. The DHEA treatment also caused a slight increase in plasma T. Exogenous DHEA may have been metabolized to sex steroids within the brain to exert these behavioral and neural effects, and it is also possible that peripheral metabolism contributed to these effects. These are the first results to suggest that exogenous DHEA increases male-male aggression and the size of an entire brain region in adults. The data are consistent with the hypothesis that DHEA regulates territorial behavior, especially in the nonbreeding season, when plasma T is basal.     

Photoperiodic regulation of adrenal hormone secretion and aggression in female Syrian hamsters

Seasonal changes in the length of the daily photoperiod induce significant changes in social behavior. Hamsters housed in winter-like short photoperiods (SP) can express significantly higher levels of aggression than hamsters housed in long photoperiods (LP) that mimic summer. The mechanisms responsible for increasing aggressiveness in SP-exposed female hamsters are not well understood but may involve seasonal changes in the endocrine system. In experiment 1, the effects of SP exposure on the circulating levels of three adrenal hormones were determined. Short photoperiod exposure was found to significantly depress the circulating levels of cortisol and the adrenal androgen dehydropiandrosterone (DHEA) but significantly increased the circulating levels of the sulfated form of DHEA, DHEAS. Experiment 2 examined the effects of gonadal hormones on several different measures of aggression including its intensity in females housed in both long and short photoperiod. Exposure to SP resulted in high levels of aggression regardless of the endocrine state of the animal or the measure used to quantify aggression. In contrast, administration of estradiol to hamsters housed in LP significantly reduced aggression. The data of the present study support the hypothesis that SP-housed females are more aggressive than LP-housed females because SP exposure renders females insensitive to the aggression-reducing effects of ovarian hormones.     

Individual differences in estrogen receptor alpha in select brain nuclei are associated with individual differences in aggression

Steroid hormones play an important role in modulating social behavior in many species. Estrogens are thought to act on an interconnected network of hypothalamic and limbic brain areas to affect aggressive behavior, although the specific nuclei unknown remain unspecified. We show that individual variation in estrogen receptor alpha (ERalpha) immunoreactivity in the lateral septum (LS), ventral bed nucleus of the stria terminalis (vBNST), and anterior hypothalamus (AHA) of CD-1 mice is positively correlated with aggressive behavior. When males were treated with fadrozole (an aromatase inhibitor), aggressive behavior was reduced, although castration did not reduce aggression. These results suggest that estrogens modulate aggressive behavior by acting on a circuit that includes the LS, vBNST, and AHA and that the source of estrogens is non-gonadal. Fadrozole also decreased c-fos expression in the lateral septum following aggressive encounters. Although the effects of estrogen on aggression appear to involve regulation of neuronal activity in the LS, additional processes are likely involved. These results suggest that estrogen acts in a specific subset of a complex network of nuclei to affect aggressive behavior.     

VPAC receptor signaling modulates grouping behavior and social responses to contextual novelty in a gregarious finch: A role for a putative prefrontal cortex homologue

In both mammals and birds, vasoactive intestinal polypeptide (VIP) neurons and fibers are present in virtually every brain area that is important for social behavior. VIP influences aggression in birds, social recognition in rodents, and prolactin secretion in both taxa, but other possible functions in social modulation remain little explored. VIP effects are mediated by VPAC receptors, which bind both VIP and pituitary adenylate cyclase activating peptide. Within the lateral septum and medial bed nucleus of the stria terminalis, VPAC receptors are found at higher densities in gregarious finch species relative to territorial species, suggesting that VPAC receptor activation promotes social contact and/or preference for larger groups. Here we here test this hypothesis in zebra finches (Taeniopygia guttata), and also examine the relevance of VPAC receptors to anxiety-like processes. Intraventricular infusions of the VPAC receptor antagonist, neurotensin6–11 mouseVIP7–28, strongly reduce social contact when animals are tested in a novel environment, and exert sex-specific effects on grouping behavior. Specifically, VPAC receptor antagonism reduces gregariousness in females but increases gregariousness in males. Interestingly, VPAC antagonism in the medial pallium (putative prefrontal cortex homologue) significantly reduces gregariousness in both sexes, suggesting site-specific effects of VIP signaling. However, VPAC antagonism does not modulate novel-familiar social preferences in a familiar environment or general anxiety-like behaviors. The current results suggest that endogenous activation of VPAC receptors promotes social contact under novel environmental conditions, a function that may be accentuated in gregarious species. Moreover, endogenous VIP modulates gregariousness in both males and females.     

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase

Pregnenolone and dehydroepiandrosterone (DHEA) are sex hormone precursors and neuroprotective steroids. Effects of pregnenolone and DHEA may be in part mediated by their conversion to testosterone and by the consecutive conversion of testosterone to estradiol by the enzyme aromatase. This enzyme is induced in reactive astrocytes after different forms of neurodegenerative lesions and the resultant local production of estradiol in the brain has been shown to be neuroprotective. The participation of aromatase in the neuroprotective effect of pregnenolone and DHEA has been assessed in this study. The protective effect of different doses (12.5, 25, 50, and 100 mg/kg) of pregnenolone or DHEA, against systemic kainic acid (7 mg/kg b.w.), was assessed on hippocampal hilar neurons in gonadectomized Wistar male rats. To determine whether the neuroprotective effect of pregnenolone and DHEA was dependent on their conversion to estradiol, the aromatase inhibitor fadrozole (4.16 mg/ml) was administered using subcutaneous osmotic minipumps. The number of Nissl-stained neurons in the hilus of the dentate gyrus of the hippocampal formation was estimated by the optical disector method. The administration of kainic acid resulted in a significant decrease in the number of hilar neurons compared to rats injected with vehicles. Pregnenolone and DHEA showed a dose-dependent protective effect of hilar neurons against kainic acid. The administration of the aromatase inhibitor fadrozole blocked the neuroprotective effect of pregnenolone and DHEA. These findings suggest that estradiol formation by aromatase mediates neuroprotective effects of pregnenolone and DHEA against excitotoxic-induced neuronal death in the hippocampus.     

Impact of season and social challenge on testosterone and corticosterone levels in a year-round territorial bird

Plasma testosterone increases during breeding in many male vertebrates and has long been implicated in the promotion of aggressive behaviors relating to territory and mate defense. Males of some species also defend territories outside of the breeding period. For example, the European nuthatch (Sitta europaea) defends an all-purpose territory throughout the year. To contribute to the growing literature regarding the hormonal correlates of non-breeding territoriality, we investigated the seasonal testosterone and corticosterone profile of male (and female) nuthatches and determined how observed hormone patterns relate to expression of territorial aggression. Given that non-breeding territoriality in the nuthatch relates to the reproductive context (i.e., defense of a future breeding site), we predicted that males would exhibit surges in plasma testosterone throughout the year. However, we found that males showed elevated testosterone levels only during breeding. Thus, testosterone of gonadal origin does not appear to be involved in the expression of non-breeding territoriality. Interestingly, territorial behaviors of male nuthatches were stronger in spring than in autumn, suggesting that in year-round territorial species, breeding-related testosterone elevations may upregulate male-male aggression above non-breeding levels. In females, plasma testosterone was largely undetectable. We also examined effects of simulated territorial intrusions (STIs) on testosterone and corticosterone levels of breeding males. We found that STIs did not elicit a testosterone response, but caused a dramatic increase in plasma corticosterone. These data support the hypothesis that corticosterone rather than testosterone may play a role in the support of behavior and/or physiology during acute territorial encounters in single-brooded species.     

Aggression, dominance, and affiliation: Their relationships with androgen levels and intelligence in 5-year-old children

This study explores the potential relationship between social behavior (aggression, dominance, and affiliation) and testosterone, androstenedione, and DHEA measurements in 5-year-old children while also analyzing the moderating effect of IQ on the hormone-behavior relationship. 129 healthy normal Iberian children (60 boys and 69 girls) were videotaped in free play interactions in the school playground. Their behavior was then evaluated with particular emphasis on aggression, government, and affiliation. Testosterone, androstenedione, and DHEA levels were measured using an enzyme immunoassay technique in saliva samples. A test (K-BIT) which provides an IQ measurement for children was also administered to subjects. The correlation analysis revealed a positive relationship between the behavioral factor of Provocation and androstenedione in boys, and a regression analysis indicated that this relationship was moderated in a positive direction by the subject's intelligence. In girls, we observed a positive relationship between testosterone and Affectivity, with this relationship being moderated in a negative direction by intelligence.     

A Potential Role for 5‐Androstene‐3β,7β,17β‐triol in Obesity and Metabolic Syndrome

Metabolic syndrome is marked by perturbed glucocorticoid (GC) signaling, systemic inflammation, and altered immune status. Dehydroepiandrosterone (DHEA), a major circulating adrenal steroid and dietary supplement, demonstrates antiobesity, anti‐inflammatory, GC‐opposing and immune‐modulating activity when administered to rodents. However, plasma DHEA levels failed to correlate with metabolic syndrome and oral replacement therapy provided only mild benefits to patients. Androstene‐3β,7β,17β‐triol (β‐AET) an anti‐inflammatory metabolite of DHEA, also exhibits GC‐opposing and immune‐modulating activity when administered to rodents. We hypothesized a role for β‐AET in obesity. We now report that plasma levels of β‐AET positively correlate with BMI in healthy men and women. Together with previous studies, the observations reported here may suggest a compensatory role for β‐AET in preventing the development of metabolic syndrome. The β‐AET structural core may provide the basis for novel pharmaceuticals to treat this disease.     

Neuroendocrine correlates of behavioral polymorphism in white-throated sparrows

Interspecific differences in the neuropeptide systems of the lateral septum (LS) often parallel differences in social behavior. In rodents, some closely related species that differ in aggressive behavior also differ according to the level of vasopressin (VP) innervation of the LS. In songbirds, the neuropeptides vasotocin (VT) and vasoactive intestinal peptide (VIP) affect aggression when administered directly to the LS. Here, we tested whether the density of VT or VIP innervation of the LS reflects patterns of intraspecific behavioral polymorphism in male and female white-throated sparrows (Zonotrichia albicollis), in which the "white-stripe" (WS) morph behaves more aggressively than the "tan-stripe" (TS) morph. We found that the WS birds had more VT-immunoreactivity (IR) than the TS birds in the ventrolateral subdivision of the caudal LS (LSc.vl) and in the medial portion of the bed nucleus of the stria terminalis (BSTm). In addition, the TS birds had more densely stained VIP-IR in the LSc.vl than the WS birds. Males had more VT-IR than females in the LSc.vl and BSTm, and more VIP-IR in the LSc.vl. We also report sex and morph differences in VIP-IR in the basal hypothalamus, where VIP is synthesized and released into the portal vasculature. Males had nearly twice as many VIP-immunoreactive (ir) neurons in the infundibular nucleus than did females, and birds of the WS morph had more densely stained VIP-IR in the median eminence than TS birds. Our results support the hypothesis that differences in these neuropeptide systems underlie inter- and intraspecific differences in social behavior across vertebrates.     

Species differences in paternal behavior and aggression in peromyscus and their associations with vasopressin immunoreactivity and receptors.

Previous comparative studies have suggested that the distribution of arginine vasopressin (AVP) pathways within the brain is associated with species-typical patterns of social behavior. In the current study, male parental behavior and aggression were compared in two species of Peromyscus. As predicted based on other studies, male mice from a monogamous species, the California mouse Peromyscus californicus, spent more time providing parental care to offspring than males from a polygamous species, the white-footed mouse Peromyscus leucopus. Sexually naive male California mice also attacked opponents more rapidly than white-footed mice during resident-intruder and neutral aggression tests. Since AVP has been shown to modulate these behaviors, we compared the distribution of vasopressinergic neurons and receptors. We predicted that greater AVP-immunoreactive (AVP-ir) staining in the bed nucleus of the stria terminalis and AVP receptor density in the lateral septum would occur in the species with low levels of paternal care because this pattern was found in similar comparisons with sexually naive monogamous and polygamous voles. In contrast, in our study, monogamous male mice showed more AVP-ir staining in the bed nucleus of the stria terminalis than the polygamous species, as well as more AVP receptors in the lateral septum. Parental behavior therefore does not appear to predict differences in patterns of AVP-ir staining and receptor distribution across species or vice versa. We propose the hypothesis that aggression may be better correlated with species patterns of AVP-ir staining density and receptor distribution.     

The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens

Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short ‘winter-like'' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a ‘seasonal switch’ from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.     

Aggressive interactions differentially modulate local and systemic levels of corticosterone and DHEA in a wild songbird

During the nonbreeding season, when gonadal androgen synthesis is basal, recent evidence suggests that neurosteroids regulate the aggression of male song sparrows. In particular, dehydroepiandrosterone (DHEA) is rapidly converted in the brain to androgens in response to aggressive interactions. In other species, aggressive encounters increase systemic glucocorticoid levels. However, the relationship between aggression and local steroid levels is not well understood. Here, during the breeding and nonbreeding seasons, we tested the effects of a simulated territorial intrusion (STI) on DHEA and corticosterone levels in the brachial and jugular plasma. Jugular plasma is enriched with neurosteroids and provides an indirect index of brain steroid levels. Further, during the nonbreeding season, we directly measured steroid levels in the brain and peripheral tissues. Both breeding and nonbreeding males displayed robust aggressive responses to STI. During the breeding season, STI increased brachial and jugular corticosterone levels and jugular DHEA levels. During the nonbreeding season, STI did not affect plasma corticosterone levels, but increased jugular DHEA levels. During the nonbreeding season, STI did not affect brain levels of corticosterone or DHEA. However, STI did increase corticosterone and DHEA concentrations in the liver and corticosterone concentrations in the pectoral muscle. These data suggest that 1) aggressive social interactions affect neurosteroid levels in both seasons and 2) local steroid synthesis in peripheral tissues may mobilize energy reserves to fuel aggression in the nonbreeding season. Local steroid synthesis in brain, liver or muscle may serve to avoid the costs of systemic increases in corticosterone and testosterone.     

Distinct correlations of vasopressin release within the lateral septum and the bed nucleus of the stria terminalis with the display of intermale aggression

Arginine vasopressin (AVP) has been implicated in a wide variety of social behaviors ranging from affiliation to aggression. However, the precise functional involvement of AVP in intermale aggression is still a matter of debate. In fact, very little is known about AVP release patterns within distinct brain regions during the display of intermale aggression and, in turn, the behavioral consequences of such release. We used intracerebral microdialysis to monitor local AVP release within the lateral septum (LS) and the bed nucleus of the stria terminalis (BST) of adult male Wistar rats during the resident-intruder (RI) test. Resident males were cohabitated with a female prior to the RI test to stimulate intermale aggression toward the intruder male. AVP release within the LS correlated positively with intermale aggression. The specific AVP V1a receptor antagonist d(CH₂)₅Tyr(Me)AVP (10 μg/ml) administered via retrodialysis (3.3 µl/min, 30 min) into the LS of high-aggressive rats prior to the second RI test, prevented an increase in aggression in the second compared with the first RI test as seen in vehicle-treated high-aggressive rats. In contrast to the LS, AVP release within the BST correlated negatively with intermale aggression. Moreover, retrodialysis of synthetic AVP (1 µg/ml) administered into the BST of high-aggressive rats significantly reduced the display of aggression during the second RI test. These data reveal that AVP can both promote and inhibit intermale aggression, depending upon the brain region in which AVP is released. Although challenging the general view that central AVP release enhances intermale aggression in rodents, our data support a model in which AVP coordinates a range of social behaviors by eliciting region-specific effects.     

Sex differences due to dehydroepiandrosterone (DHEA) feeding affecting dehydroepiandrosterone sulfate secretion in golden Syrian hamsters.

The metabolism of orally administered dehydroepiandrosterone (DHEA) by male and female golden Syrian hamsters was examined by quantification of DHEA and dehydroepiandrosterone sulfate (DHEAS) in gallbladder bile, urine and feces using high-performance liquid chromatography (HPLC). Plasma levels of DHEA and DHEAS were also determined by radioimmunoassay (RIA). After 5 days of oral DHEA administration (100 mg/kg body weight twice a day), RIA showed that plasma levels of DHEA and DHEAS were increased approximately 3-6 and 4-5 times, respectively, compared to controls. More than 95 % of circulating DHEA (S) in the peripheral blood was DHEAS. There was no significant sex difference in DHEAS plasma levels between male and female animals in the DHEA-supplemented group. However, 0.2 - 0.3 % of ingested DHEA was conjugated to DHEAS and excreted in urine by females, whereas less than 0.002 % was excreted in urine by males (p < 0.005). DHEAS was excreted in bile by males after DHEA supplementation, and the sex differences in DHEAS levels observed in bile were statistically significant (male, 18.7 +/- 7.5 vs. female, 5.6 +/- 3.1 micromol/l) (p < 0.005). Small amounts of ingested DHEA were excreted in an unchanged state in feces, and no sex difference was observed. These results suggest that there is a considerable sex difference in the conjugation and excretion of orally administered DHEA in the hamster.     

Glutamic acid decarboxylase (GAD65) immunoreactivity in brains of aggressive, adolescent anabolic steroid-treated hamsters

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent AAS exposure influenced the immunohistochemical localization of glutamic acid decarboxylase (GAD65), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), in areas of hamster brain implicated in aggressive behavior. Hamsters were administered high dose AAS throughout adolescence, scored for offensive aggression, and then examined for differences in GAD65 puncta to regions of the hamster brain important for aggression. When compared with control animals, aggressive AAS-treated hamsters showed significant increases in the area covered by GAD65 immunoreactive puncta in several of these aggression regions, including the anterior hypothalamus, ventrolateral hypothalamus, and medial amygdala. Conversely, aggressive AAS-treated hamsters showed a significant decrease in GAD65-ir puncta in the lateral septum when compared with oil-treated controls. However, no differences in GAD65 puncta were found in other aggression areas, such as the bed nucleus of the stria terminalis and central amygdala. Together, these results support a role for altered GAD65 synthesis and function in adolescent AAS-facilitated offensive aggression.