Non-reproductive Behaviors Research Articles

The emergence of gonadal hormone influences on dopaminergic function during puberty

Adolescence is the developmental epoch during which children become adults—intellectually, physically, hormonally and socially. Brain development in critical areas is ongoing. Adolescents are risk-taking and novelty-seeking and they weigh positive experiences more heavily and negative experiences less than adults. This inherent behavioral bias can lead to risky behaviors like drug taking. Most drug addictions start during adolescence and early drug -taking is associated with an increased rate of drug abuse and dependence. The hormonal changes of puberty contribute to physical, emotional, intellectual and social changes during adolescence. These hormonal events do not just cause maturation of reproductive function and the emergence of secondary sex characteristics. They contribute to the appearance of sex differences in non-reproductive behaviors as well. Sex differences in drug use behaviors are among the latter. The male predominance in overall drug use appears by the end of adolescence, while girls develop the rapid progression from first use to dependence (telescoping) that represent a female-biased vulnerability. Sex differences in many behaviors including drug use have been attributed to social and cultural factors. A narrowing gap in drug use between adolescent boys and girls supports this thesis. However, some sex differences in addiction vulnerability reflect biologic differences in brain circuits involved in addiction. The purpose of this review is to summarize the contribution of sex differences in the function of ascending dopamine systems that are critical to reinforcement, to briefly summarize the behavioral, neurochemical and anatomical changes in brain dopaminergic functions related to addiction that occur during adolescence and to present new findings about the emergence of sex differences in dopaminergic function during adolescence.

Aromatase in the Brain: Not Just for Reproduction Anymore

Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

The Brain as the Engine of Sex Differences in the Organization of Movement in Rats

Sex differences in the kinematic organization of non-reproductive behavior are often relegated to byproducts of sex differences in body morphology. We review evidence showing not only that male and female rats organize their posture and stepping differently during a variety of actions, but that these differences arise from sex differences in the organization of movement in the central nervous system (CNS). Indeed, the expression and choice of sex-typical patterns of movement can be altered by CNS injury. The pattern of hormonal regulation of these sex differences is also not organized as commonly held theory would predict. As expected, males castrated shortly after birth are female-typical in their motor organization. Females ovariectomized at birth, however, are male-typical in their patterns of movement. Thus, female-typical patterns of movement organization are not the default form, but rather are dependent on the effects of gonadal steroids to feminize the developing CNS. The implications of these findings are discussed with regards to our understanding of the evolution of sex differences in CNS anatomy and behavior both for animals and humans.

Amniotic fluid testosterone: relationship with cortisol and gestational age

Foetal exposure to testosterone is increasingly implicated in the programming of future reproductive and non-reproductive behaviour. Some outcomes associated with prenatal exposure to testosterone may be predicted from exposure to prenatal stress, suggesting a link between them. The peak serum levels of testosterone in the foetus are thought to be around 14-18 weeks' gestation, and we explored testosterone levels at different gestations. Although best investigated in foetal plasma, this is now difficult because of the decline in frequency of foetal blood sampling; in this study, we used amniotic fluid as a biomarker to investigate foetal exposure. To investigate the relationship between amniotic fluid testosterone, amniotic fluid cortisol, foetal gender, and gestational age. Paired amniotic fluid and maternal plasma samples were collected from 264 pregnant women undergoing amniocentesis between 15 and 37 weeks' gestation (median 17 weeks [119 days]). Total testosterone and cortisol in amniotic fluid, and total plasma testosterone (maternal) were measured by radioimmunoassay. Amniotic fluid testosterone levels were higher in male than in female foetuses, with a median (interquartile range) of 0.85 nmol/l (0.60-1.17 nmol/l) and 0.28 nmol/l (0.175-0.45 nmol/l), respectively. No relationship between amniotic fluid testosterone and gestational age was detected in either sex. Amniotic fluid testosterone correlated positively with amniotic fluid cortisol in both sexes (r = 0.30 male foetuses, r = 0.33 female foetuses, P < 0.001 for both), and remained significant in multivariate analysis. Testosterone in amniotic fluid did not change with gestation in the second and third trimester, raising questions about the timing of the reported early peak in the male foetus. The positive correlation between cortisol and testosterone in amniotic fluid suggests that increased foetal exposure to cortisol may also be associated with increased exposure to testosterone.

Maternal experience inhibits the production of immature neurons in the hippocampus during the postpartum period through elevations in adrenal steroids

Motherhood is accompanied by alterations in numerous nonreproductive behaviors, including learning and memory, as well as anxiety and stress regulation. These functions have been linked to adult neurogenesis in the hippocampus, but the effect of maternal experience on this brain region has not been completely explored. To determine whether the production of new hippocampal granule cells is altered during the postpartum period, we examined the number of proliferating cells and their progeny in the dentate gyrus of primiparous female rats at various time points during the postpartum period while they were caring for their offspring, as well as after weaning. Additionally, we investigated whether cell proliferation in the postpartum female is affected by the presence of offspring and nursing-induced increases in glucocorticoids. Analysis of the number of BrdU-labeled cells revealed that cell proliferation in the dentate gyrus was suppressed in lactating postpartum females until the time of weaning. This effect was temporary; a difference was detectable at 1 week after BrdU-labeling, when the majority of cells expressed a marker of immature and mature granule neurons (TuJ1) but not at 2 weeks, when most cells expressed a marker of mature neurons (NeuN). The decrease in cell proliferation was dependent on elevated basal glucocorticoid levels associated with lactation; removal of nursing pups reduced basal corticosterone levels and prevented the decrease in the number of BrdU-labeled cells. Moreover, preventing increased basal corticosterone levels by means of adrenalectomy and low-dose corticosterone replacement eliminated the reduction in cell proliferation. These findings indicate that offspring interactions inhibit adult neurogenesis through changes in adrenal steroids, and further suggest a potential mechanism for alterations in hippocampal function during the postpartum period.

Effects of a pyrethroid pesticide on endocrine responses to female odours and reproductive behaviour in male parr of brown trout ( Salmo trutta L.)

Reproductive behaviour of brown trout ( Salmo trutta L.) from an anadromous stock was studied in a large stream water aquarium. Four adult males and two ovulated females were placed in the aquarium together with eight mature male parr. Four of the parr were exposed during the previous 4 days to two concentrations (0.1 or 1.0 μg l −1) of the pyrethroid pesticide cypermethrin (a disrupter of olfactory receptor function) and four of the parr to the solvent ethanol. The behaviour of all fish was followed for 24 h and then blood and milt was collected. Exposure to the higher concentration of cypermethrin disturbed the reproductive behaviour of the parr. They displayed fewer courting events, spent less time near the nesting females and had lower volumes of strippable milt. They also had significantly lower amounts of 11-ketotestosterone (11-KT) in the blood plasma than the control group. The higher cypermethrin group also had significantly lower levels of all these variables than the lower cypermethrin group, apart from strippable milt that showed no significant differences between two groups. No significant differences in non-reproductive behaviours were observed between any of the groups. In the control fish, there were significant positive correlations between (a) the number of courting events and the amount of time spent near the female, (b) blood plasma levels of 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) and time spent near the female and (c) plasma levels of 17,20β-P and the number of courting events. Further, in control fish, higher plasma levels of 17,20β-P were observed in parr interacting with a female compared to those with no female contacts. A priming experiment confirmed a previous study that cypermethrin damages olfactory reception. Parr exposed to cypermethrin had significantly lower blood plasma levels of 17,20β-P and 11-KT than control males after exposure to ovarian fluid and urine (known to contain reproductive priming pheromones). When ethanol-exposed males were exposed to ovarian fluid and urine they had significantly higher plasma levels of 17,20β-P compared to those exposed to water only.

Effects of dietary methylmercury on reproductive behavior of fathead minnows (Pimephales promelas)

We examined the effects of dietary methylmercury on the production of testosterone in and the reproductive behavior of male fish. Juvenile fathead minnows (Pimephales promelas) were fed one of three diets contaminated with methylmercury at concentrations of 0.06 (control), 0.87 (low), and 3.93 (medium) microg Hg/g dry weight. After attaining sexual maturity, fish were paired for mating, and male behaviors were recorded. Carcass mercury and plasma testosterone concentrations also were measured. No significant differences were found in the amount of time spent by male fish in nest preparation or courtship activities, but dietary methylmercury suppressed mating behavior. Fish that were fed control diets spent approximately 5% of their time spawning; fish that were fed methylmercury-contaminated diets spent approximately 0.5% of their time spawning. Total mercury concentration in the carcass was not correlated with any individual reproductive behavior but was correlated with hypoactivity. Fish that were fed the low- and medium-methylmercury diets and with mean carcass concentrations of 0.71 to 4.2 microg Hg/g dry weight spent an average of 19 to 26% of their time being inactive; control fish with an average of 0.07 microg Hg/g dry weight spent only 8% of their time being inactive. No significant difference was found in testosterone concentrations among dietary treatments; however, testosterone was positively correlated with individual nest preparatory, courtship, and spawning behaviors and negatively correlated with the total amount of time spent in all nonreproductive behaviors. The relation between testosterone, reproductive behavior, and spawning success suggests that altered behavior is, in part, responsible for suppression of reproduction in methylmercury-exposed fish. Moreover, reproductive behavior may be more sensitive than steroid hormones to alteration by dietary methylmercury.

Estradiol and Tryptophan Depletion Interact to Modulate Cognition in Menopausal Women

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.

Developmental exposure to environmental estrogens alters anxiety and spatial memory in female mice

Humans and wildlife are exposed to numerous anthropogenic drugs and pollutants. Many of these compounds are hormonally active, and recent evidence suggests that the presence of these endocrine disruptors permanently alters normal development and physiology in a variety of vertebrate species. Here, we report on the effects of developmental exposure to two common estrogenic pollutants, bisphenol A and ethinyl estradiol on sexually dimorphic, non-reproductive behavior. Mice ( Mus musculus domesticus) were exposed to environmentally relevant levels of these chemicals (2 and 200 μg/kg/day for bisphenol A and 5 μg/kg/day for ethinyl estradiol) throughout prenatal and early postnatal development. As adults, the animals were observed in a variety of tests measuring sexually dimorphic behaviors including short-term spatial memory (in a radial-arm maze and a Barnes maze) and anxiety (in an elevated-plus maze and a light/dark preference chamber). Developmental exposure to ethinyl estradiol was found to masculinize behavior in all of the assays used. Bisphenol A increased anxious behavior in a dose-dependent fashion but had no effect on spatial memory. These results indicate that non-reproductive, sexually dimorphic behavior is sensitive to endocrine disruption. In addition, these experiments suggest that both humans and wildlife are being exposed to levels of these endocrine disrupting compounds that are sufficient to disrupt the development of the nervous system and that may have permanent consequences on sexually dimorphic behaviors.

Screening of food extracts for estrogenic activity

Estrogens though well known for their reproductive role are important regulators of mood. Estrogen (mainly 17β-estradiol) mediates its actions through two main intracellular receptors- estrogen receptors α and β(ERα and ERβ). ERβ mediated signalling appears to be critical in regulating nonreproductive behaviour such as processing of emotional behaviour and cognitive functions such as verbal fluency, memory and learning. Phytoestrogens and other natural plant extracts are now increasingly being studied for their anxiolytic properties. We have set up a three-tiered system to assay the reactivity of plant extracts to ERβ – assay of the physical binding affinity of extracts to ERβ based on a receptor binding assay. assay of the estrogenic response as evidenced by proliferation of the estrogen-dependent MCF-7 cells. And quantitation of the ERα and ERβ gene expression in MCF-7 cells treated with the extracts. Fruit extracts from apples, kiwifruit and various berries, as well as standard polyphenols and essential oils were screened. Apple extract, berry extract, eugenol, geraniol, farnesene and standard polyphenols such as naringenin and genistein demonstrated an estrogenic response. This has implications for their uses in delivering estrogen associated cognitive benefits in functional foods. Funded by the Foundation for Research, Science and Technology, New Zealand.

Indirect consequences of parental care: sex differences in ectoparasite burden and cleaner-seeking activity in longfin damselfish

Many direct costs of parental care have been described for teleost fishes, including reduced body weight, body fat and immune condition. However, few studies have focussed on the indirect consequences of reproduction. In this study, we investigated such consequences in the longfin damselfish Stegastes diencaeus (Jordan & Rutter), a territorial reef fish in which the males provide parental care of eggs. More specifically, we examined patterns of spatial distribution of males and females in relation to substratum suitability for the establishment of nest sites and the consequences of spatial distribution for ectoparasite burden and cleaner-seeking activity. The territories of males and females differed significantly in a number of habitat features. Breeding males, with a nest site present in their territory, were found mainly at the periphery of reef patches, near sand, where vertical substratum suitable for nest sites is present, whereas females and non-breeding males were found in the centre of patches. Cleaning stations occupied by the cleaning gobies Elacatinus evelynae and E. prochilos were also located in peripheral areas, thus, in general, breeding males were closer to cleaning stations than females. Damselfish that were closer to cleaning stations visited them more frequently. During nest-guarding periods, males visited cleaning stations less frequently than during non-guarding periods, but this was not concomitant with an increase in ectoparasite loads during nest-guarding periods. Damselfish in peripheral territories had significantly lower ectoparasite numbers than those situated in the centre of reef patches. These results are consistent with a lower exposure of peripheral damselfish to ectoparasites. These intersexual differences in territory position, proximity to and use of cleaning stations, and ectoparasite loads are indirect consequences of sex differences in reproductive-resource requirements. Such interactions between breeding systems, distributional ecology and other aspects of non-reproductive behaviour are undoubtedly widespread, and their consideration could enhance our general understanding of reef-fish ecology.

Sexually dimorphic nonreproductive behaviors as indicators of endocrine disruption.

Measures of cognitive and other behaviors not specifically related to reproduction are often sex-linked. Males and females perform differently on many tasks and often interact with members of their species in dissimilar ways. If such differences are diminished, reversed, or widened by prenatal chemical exposures, a reasonable inference is that exposure interfered with sexual differentiation of the brain, largely, but not exclusively, through interference with the actions of gonadal hormones. Explicit recognition of sex differences in performance is not a prominent feature of toxicity testing, however, except for reproduction studies, and is not a recognized criterion in developmental neurotoxicity testing. In contrast to the low visibility accorded sex differences in testing protocols for the assessment of developmental neurotoxicity, the literature is filled with examples showing that the developing male and female respond differently to many chemical agents, with subsequent expression in behavior. Quite often, even when such differences are reported, further analyses are not carried out nor are subsequent studies conducted for clarification. Moreover, many investigators include only male subjects. Both polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) studies provide several examples of striking differences between the behavioral responses of male and female offspring to developmental exposure. They offer examples, as well, of how to approach the study and analysis of such differences. Given the societal importance of risk assessments applied to potential developmental neurotoxicants, studies should be deemed questionable if they fail to include outcome measures based on sexual dimorphisms in nonreproductive behaviors.

Effects of Estrogen on Activity and Fear-Related Behaviors in Mice

Estrogen has been shown to affect nonreproductive behaviors in humans and rodents, including anxiety, fear, and activity levels. Rat studies have shown increases and decreases in these behaviors. Inconsistencies may be due to differences in testing conditions and the extent to which each test measures anxiety, fear, or activity. Few mouse studies have been performed. The present study was conducted to address these issues by examining the effect of estradiol benzoate (EB) in ovariectomized (OVX), C57BL/6 mice on a range of behavioral paradigms measuring anxiety [open field (OF), dark–light transition (DLT), elevated plus maze (EP)], activity [running wheel (RW)], and conditioned fear learning (FCon). In OF, vehicle (Veh) animals spent more time in the center than EB-treated animals and were more active overall. In DLT, Veh animals were more active than EB-treated animals in both the dark and light compartments and made more transitions between the two. In EP, Veh animals entered a greater number of arms. During FCon, EB animals froze more than Veh to the conditioned stimulus. In contrast, in the home cage RW, EB animals were more active than Veh. Factor analysis was used to characterize intertask correlations of females' behavior and to explore the possibility that estrogen may have an impact on a general arousal factor. In sum, estrogen treatment heightened fear responses in a range of fear and anxiety-provoking situations (OF, DLT, EP, and FCon), while increasing activity in the safer RW. We suggest that EB treatment may result in a generally more aroused animal.

Behavioral responses of rats exposed to long-term dietary vinclozolin.

Vinclozolin is a fungicide used on food crops with human exposure estimated at approximately 2 microg/kg/day from ingestion; occupational exposure, however, may be greater. The metabolites of vinclozolin have been reported to act as antiandrogens and have adverse effects on reproductive physiology and behavior in animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or 750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult) beginning on gestational day 7, and offspring were continued on these diets through sacrifice at postnatal day 77. Male and female offspring were assessed for changes in several nonreproductive sexually dimorphic behaviors: open field and running wheel locomotor activity, play behavior, and consumption of saccharin- and sodium chloride-flavored solutions. There was a significant interaction of sex with vinclozolin exposure on running wheel activity, which indicated that females in the high-dose exposure group were hypoactive compared to same-sex controls. There was a significant overall effect of vinclozolin exposure on fluid consumption, and high-dose animals showed increased intake of the saccharin solution and decreased intake of plain water while saccharin was available. Effects were more pronounced in females, which drank 40.8% more saccharin than control females, whereas males drank 6.2% more than control males. There were no effects of vinclozolin treatment on play behavior or sodium solution intake. Gestational duration, total and live pups per litter, litter sex ratios, and birth weight were also not significantly affected, nor were body weight and food intake for dams and offspring. These results indicate that long-term dietary exposure to vinclozolin does not have severe toxicological consequences on the nonreproductive behaviors measured here. However, exposure may cause subtle alterations in locomotor activity and consumption of saccharin-flavored solution.

Perspectives on gender differences in food intake and frequency of disease

Sex differences in many non-reproductive behaviors have been described in rodents and humans. Among the behaviors and responses that are sexually dimorphic in the rat are: activity, aggression, pain, and taste sensitivity, food intake and body weight regulation, learning and retention of certain kind of mazes, avoidance response, taste aversion, and performance on schedule reinforcement. In humans, similar sex differences are seen in verbal fluency, performance of spatial tasks, verbal memory tests, and fine motor skills. Depression and depressive diseases are more common in women while substance abuse and antisocial behavior is more common in men. Immunologically, the female sex is stronger, and there are clear gender differences in outcomes to same treatment modalities. This review examines the sexual dimorphism in non-reproductive behavior. Specifically gender differences in central mechanisms of food intake regulation including gender differences in hypothalamic monoaminergic systems influencing food intake.

Sex Steroids and Human Behavior: Implications for Developmental Psychopathology

In a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.

Spatial ability of XY sex-reversed female mice

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y POS consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y POS strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.

Influence of a natural stressor (predator odor) on locomotor activity in the meadow vole (Microtus pennsylvanicus): modulation by sex, reproductive condition and gonadal hormones.

Sex differences in a variety of non-reproductive behaviors have been indicated to occur in seasonally breeding polygynous promiscuous rodents such as the meadow vole, Microtus pennsylvanicus. The present study was designed to assess the effects of reproductive and hormonal status on the locomotor responses of meadow voles following brief exposure to the odors of a natural predator, the Red fox (Vulpes vulpes). Adult male and female meadow voles, which are seasonal photoperiodically-induced breeders, were housed in either mixed sex pairs under a long, reproductively stimulatory photoperiod (simulating breeding: long light cycle, paired: LLC + P) or in same-sex pairs under a short, reproductively inhibitory photoperiod (simulated non-breeding: short light cycle, non-paired: SLC-NP). On 2 consecutive days following 1 day of baseline activity monitoring, voles were exposed individually for 3 min to fox odor and a novel pungent control odor (extract of almond). The levels of various measures of activity that were displayed by the voles were assessed by an automated Digiscan activity monitoring system. LLC + P (simulated breeding) voles displayed higher basal levels of activity relative to SLC + NP (simulated non-breeding) voles, with males displaying greater activity than females. LLC + P (simulated breeding) males displayed a significant reduction in activity levels following exposure to fox odor relative to control odor. The reductions in activity following fox odor exposure were related to plasma testosterone levels such that a larger behavioral response (i.e. greater reduction) was associated with higher levels of testosterone. Furthermore, dividing males into high and low testosterone groups based on the median levels of testosterone revealed that high but not low testosterone males displayed reductions in activity following exposure to fox odor relative to control odor. No changes in activity levels following exposure to fox odor were noted in SLC-NP males, and either SLC-NP or LLC + P females. These results show that this sexually dimorphic non-reproductive behavior is significantly influenced by reproductive condition and gonadal hormone levels.

Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice.

Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ERalpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ERbeta, demanded that we examine the possible participation of ERbeta in regulation of these behaviors. In dramatic contrast to our results with ERalpha knockout (alphaERKO) males, betaERKO males performed at least as well as wild-type controls in sexual behavior tests. Moreover, not only did betaERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience. These data revealed a significant interaction between genotype and social experience with respect to aggressive behavior. Finally, females lacking a functional beta isoform of the ER gene showed normal lordosis and courtship behaviors, extending in some cases beyond the day of behavioral estrus. These results highlight the importance of ERalpha for the normal expression of natural reproductive behaviors in both sexes and also provide a background for future studies evaluating ERbeta gene contributions to other, nonreproductive behaviors.

Estrogen-regulated non-reproductive behaviors and breast cancer risk: animal models and human studies.

The possible role of personality patterns and psychosocial factors in breast cancer has been studied extensively, through both human and animal experiments. The data are conflicting, and the conclusions controversial. This review will serve two purposes. First, we present evidence that behavioral patterns most commonly linked to breast cancer risk are at least partly regulated by estrogens. This section will suggest that some estrogen-regulated behaviors may be markers of increased breast cancer risk. Second, we will briefly review recent findings in animals connecting psychosocial factors to cancer. We also will address the plausible biological mechanisms. The literature suggests that estrogens, particularly when exposure occurs during the critical developmental periods, such as in utero, puberty, pregnancy, and menopause, influence affective behaviors and increase breast cancer risk. The affective behaviors include depression, aggression, and alcohol intake. Thus, psychosocial and personality factors do not necessarily have a direct impact on breast cancer risk; instead, estrogens have a dual effect on behavior and on the breast.