Social environment and anogenital distance length phenotype interact to explain testosterone levels in a communally rearing rodent: Part 1: The male side.

In vertebrates, male testosterone levels vary across the year being generally higher during the mating season relative to the offspring rearing season. However, male testosterone levels may also be associated with male anogenital distance (AGD) length (a proxy of prenatal androgen exposition), and influenced by the social group environment. In social species, it has been proposed that high levels of testosterone could be incompatible with the development of an amicable social environment. Thus, in these species, it is predicted that males have relatively low levels of testosterone. Our goal was to examine the potential association between male serum testosterone levels, season, male AGD length, and the social environment in the rodent Octodon degus under natural conditions. We quantified male serum testosterone levels during the mating and offspring rearing seasons, and we determined the number of females and males in each social group, as well as the composition of groups, in terms of the AGD length of the female and male group mates, from 2009 to 2019. Our results revealed that male testosterone levels covary with season, being highest during the offspring rearing season. Additionally, male testosterone levels vary with male AGD length, and female and male social group environments. More importantly, male degus exhibit low levels of testosterone that are indistinguishable from female levels during offspring rearing season. Similar to other highly social mammals, where males and females live together year-round, male amicable behavior could be the best male mating strategy, thus leading to a reduction in circulating testosterone levels.

Social environment and anogenital distance length phenotype interact to explain testosterone levels in a communally rearing rodent: Part 2: The female side.

Testosterone is known as a "male" hormone; however, females also synthetize testosterone, which influences female sexual and aggressive behavior. In female vertebrates, as in males, testosterone levels can vary seasonally. However, female testosterone levels may also be related with female anogenital distance (AGD) length phenotype (a proxy of prenatal androgen exposure), and the social group environment. We used data from a long-term rodent study (2009-2019) in a natural population of degus (Octodon degus) to examine the potential associations between female serum testosterone levels, season, female AGD phenotype, and social group composition. We quantified female serum testosterone levels during the mating and offspring rearing seasons, and we determined the number of females and males in social groups, as well the composition of groups, in terms of the AGD of the female and male group mates. Our results indicate that female testosterone levels vary with season, being highest during the offspring rearing season. Additionally, female testosterone levels were associated with the number of male group-members and the AGD of male group-members but were not associated with female social environment and focal female AGD phenotype. Together, our results suggest that female testosterone levels are sensitive to intersexual interactions. Our results also reveal that female and male testosterone levels do not differ between the sexes, a finding previously reported only in rock hyraxes. We discuss how the complex social system of degus could be driving this physiological similarity between the sexes.

COVID-19 as a chronic stressor and the importance of individual identity: A data-driven look at academic productivity during the pandemic.

The COVID-19 pandemic impacted personal and professional life. For academics, research, teaching, and service tasks were upended and we all had to navigate the altered landscape. However, some individuals faced a disproportionate burden, particularly academics with minoritized identities or those who were early career, were caregivers, or had intersecting identities. As comparative endocrinologists, we determine how aspects of individual and species-level variation influence response to, recovery from, and resilience in the face of stressors. Here, we flip that framework and apply an integrative biological lens to the impact of the COVID-19 chronic stressor on our endocrine community. We address how the pandemic altered impact factors of academia (e.g., scholarly products) and relatedly, how factors of impact (e.g., sex, gender, race, career stage, caregiver status, etc.) altered the way in which individuals could respond. We predict the pandemic will have long-term impacts on the population dynamics, composition, and landscape of our academic ecosystem. Impact factors of research, namely journal submissions, were altered by COVID-19, and women authors saw a big dip. We discuss this broadly and then report General and Comparative Endocrinology (GCE) manuscript submission and acceptance status by gender and geographic region from 2019 to 2023. We also summarize how the pandemic impacted individuals with different axes of identity, how academic institutions have responded, compile proposed solutions, and conclude with a discussion on what we can all do to (re)build the academy in an equitable way. At GCE, the first author positions had gender parity, but men outnumbered women at the corresponding author position. Region of manuscript origin mattered for submission and acceptance rates, and women authors from Asia and the Middle East were the most heavily impacted by the pandemic. The number of manuscripts submitted dropped after year 1 of the pandemic and has not yet recovered. Thus, COVID-19 was a chronic stressor for the GCE community.

Fostered offspring develop hyper-reactive endocrine stress responses in a plural-breeding rodent, Octodon degus.

Long-term parental separation can lead to altered behavioral and physical development in human children. Rodent models are popular for studying parent-child separation, and several studies have found that maternal separation leads to chronic changes in the endocrine stress response. However, while human children are generally raised by multiple caregivers, most rodent studies utilize solitary breeding species. Therefore, we used degus (Octodon degus) as a model for studying human parental separation, as these rodents practice plural breeding and communal care. In this study, we cross-fostered degu litters at different ages (post-natal day [PND] 2, 8, and 14) to test the hypotheses that fostering affects offspring stress hormone levels in both the short- and long-term and that these impacts differ depending on the age at which offspring are fostered. We found that fostering had long-term effects, as fostered offspring had higher stress-induced cortisol levels and weaker cortisol negative feedback than non-fostered offspring at weaning age (PND28). We also found that the timing of fostering mattered, as degus fostered at PND8 had higher baseline cortisol levels the day after fostering, while degus fostered at PND2 had higher stress-induced cortisol levels at weaning. These data suggest that long-term cross-fostering has enduring impacts on the endocrine stress response in degus, therefore making them a useful model organism for investigating impacts of parental separation in humans.

Corticosterone Alters Body Weight, but Not Metabolites, during Chronic Stress.

AbstractThe stress response is partially mediated by increased levels of circulating glucocorticoids. While the stress response may be adaptive in the short term, chronically elevated levels of glucocorticoids can be pathological. We aimed to verify that chronic stress causes metabolic dysregulation via increased corticosterone (Cort) exposure by monitoring free fatty acid (FFA) concentrations (evidence of fat breakdown), uric acid concentrations (evidence of protein breakdown), and organ weights (furcular fat, abdominal fat, liver, and pectoralis muscle) in chronically stressed juvenile house sparrows (Passer domesticus). The sparrows were chronically stressed for 3 wk by applying a series of rotating mild psychological stressors. One group of birds received injections of a glucocorticoid steroidogenesis inhibitor (mitotane) and a second group received injections of a glucocorticoid receptor antagonist (RU486) halfway through the chronic stress period to test whether glucocorticoids are responsible for protein and fat catabolism during chronic stress. Toward the end of the chronic stress period, mitotane birds increased weight compared to control and RU486 birds. Contrary to expectations, we saw no differences in FFA or uric acid levels between control and mitotane birds, but RU486 temporarily decreased stress-induced uric acid levels. Neither mitotane nor RU486 significantly altered organ weights at the end of the 3 wk. In conclusion, Cort does appear to negatively affect body weight, but the mechanism does not appear to involve increased protein or lipid metabolism.

Corticosterone's roles in avian migration: Assessment of three hypotheses.

While corticosterone (CORT) is often suggested to be an important hormone regulating processes necessary for avian migration, there has been no systematic assessment of CORT's role in migration. Prior to migration, birds increase fat stores and flight muscle size to prepare for the high energetic costs associated with long-distance flight. After attaining sufficient energetic stores, birds then make the actual decision to depart from their origin site. Once en route birds alternate between periods of flight and stopovers, during which they rest and refuel for their next bouts of endurance flight. Here, we evaluate three non-mutually exclusive hypotheses that have been proposed in the literature for CORT's role in migration. (1) CORT facilitates physiological preparations for migration [e.g. hyperphagia, fattening, and flight muscle hypertrophy]. (2) CORT stimulates departure from origin or stopover sites. (3) CORT supports sustained migratory travel. After examining the literature to test predictions stemming from each of these three hypotheses, we found weak support for a role of CORT in physiological preparation for migration. However, we found moderate support for a role of CORT in stimulating departures, as CORT increases immediately prior to departure and is higher when migratory restlessness is displayed. We also found moderate support for the hypothesis that CORT helps maintain sustained travel, as CORT is generally higher during periods of flight, though few studies have tested this hypothesis. We provide recommendations for future studies that would help to further resolve the role of CORT in migration.

Onset of Daily Activity in a Female Songbird Is Related to Peak-Induced Estradiol Levels.

Research in captive birds and mammals has demonstrated that circadian (i.e., daily) behavioral rhythms are altered in response to increases in sex-steroid hormones. Recently, we and others have demonstrated a high degree of individual repeatability in peak (gonadotropin-releasing hormone [GnRH]-induced sex) steroid levels, and we have found that these GnRH-induced levels are highly correlated with their daily (night-time) endogenous peak. Whether or not individual variation in organization and activity of the reproductive endocrine axis is related to daily timing in wild animals is not well known. To begin to explore these possible links, we tested the hypothesis that maximal levels of the sex steroid hormone estradiol (E2) and onset of daily activity are related in a female songbird, the dark-eyed junco (Junco hyemalis). We found that females with higher levels of GnRH-induced E2 departed from their nest in the morning significantly earlier than females with lower stimulated levels. We did not observe a relationship between testosterone and this measure of onset of activity. Our findings suggest an interaction between an individual's reproductive endocrine axis and the circadian system and variation observed in an individuals' daily activity onset. We suggest future studies examine the relationship between maximal sex-steroid hormones and timing of daily activity onset.

Corticosterone negative feedback is weaker during spring vs. autumn migration in a songbird (Junco hyemalis).

Birds face many challenges during seasonal migrations and must make important decisions about whether to accelerate, maintain, or delay travel to their final destinations. Spring migration is likely more challenging than autumn migration as spring journeys are completed more quickly and weather conditions are harsher during this time. These differential challenges may be reflected in the endocrine stress response, as the hypothalamic-pituitary-adrenal (HPA) axis is important for both daily energetic needs and coping with stressors. Indeed, most avian studies have found that both baseline and stress-induced corticosterone (CORT) levels tend to be higher in spring migrants than in autumn migrants. We hypothesized that CORT negative feedback efficacy also differs across the season, and is likely weaker during times of year when birds must be most sensitive to stressors. We therefore predicted that CORT negative feedback efficacy would be weaker during spring vs. autumn migration as spring migrants are more likely to encounter situations where they must decide whether to turn back or delay their travel. We examined male dark-eyed juncos (Junco hyemalis) during their spring and autumn stopovers in Fargo, ND, USA. Our prediction was met as we did find that negative feedback efficacy was weaker during spring vs. autumn, although we notably did not find any seasonal differences in baseline and stress-induced CORT. We also found that spring migrants were heavier, had greater subcutaneous fat stores, and had slightly higher hematocrit compared to autumn migrants. These findings suggest that CORT negative feedback sensitivity may help migrating birds effectively cope with the differential challenges of autumn and spring migration.

Stress, sleep, and sex: A review of endocrinological research in Octodon degus.

The Common Degu (Octodon degus) is a small rodent endemic to central Chile. It has become an important model for comparative vertebrate endocrinology because of several uncommon life-history features - it is diurnal, shows a high degree of sociality, practices plural breeding with multiple females sharing natal burrows, practices communal parental care, and can easily be studied in the laboratory and the field. Many studies have exploited these features to make contributions to comparative endocrinology. This review summarizes contributions in four major areas. First are studies on degu stress responses, focusing on seasonal changes in glucocorticoid (GC) release, impacts of parental care on offspring GC responses, and fitness consequences of individual variations of GC responses. These studies have helped confirm the ecological relevance of stress responses. Second are studies exploring diurnal circadian rhythms of melatonin and sex steroids. These studies have formed important work translating circadian biology from nocturnal laboratory rodents to diurnal humans. Third are studies that exploit the open nature of degu natural habitat, combined with laboratory studies, to explore the impact of testosterone on agonistic behavior. Studies have focused primarily on male:male, female:female, male:female, and parental behaviors. Fourth, are contributions to the study of female masculinization from male siblings in the uterus. These studies have focused on both the behavioral consequences of masculinization and the impact of those behaviors on fitness. Taken together, the studies reviewed here have formed a strong foundation for further studies in the degu so that future studies can address how endocrinological components underlie new mechanistic connections to the ecological effects on behavior and fitness.

Changes in processes downstream of the hypothalamus are associated with seasonal follicle development in a songbird, the dark-eyed junco (Junco hyemalis).

Mechanisms related to seasonal reproductive timing in vertebrates have received far more study in males than in females, despite the fact that female timing decisions dictate when rearing of offspring will occur. Production and release of gonadotropin-releasing hormone (GnRH) by the hypothalamus stimulates the pituitary to secrete gonadotropins, initiating the beginning stages of gonadal recrudescence and production of the sex steroids, testosterone and estradiol, which are necessary to prime the liver for secretion of yolk precursors in breeding female birds. While stimulation by the hypothalamus can occur during the pre-breeding period, egg development itself is likely regulated downstream of the hypothalamus. We used GnRH challenges to examine variation in breeding-stage-specific patterns of pituitary and ovarian responsiveness in free-living female dark-eyed juncos (Junco hyemalis) and also examined the ovary and liver for variation in mRNA expression of candidate genes. Baseline LH levels increased during the transition from pre-breeding to egg-development, however no significant difference was observed in post-GnRH injection levels for LH or sex steroids (testosterone and estradiol). Interestingly, a stage by time-point interaction was observed, with post-GnRH LH levels increasing over baseline during the pre-breeding stage, but not during the egg-development stage. We observed a decrease in liver mRNA expression of estradiol receptor-alpha, and glucocorticoid and mineralocorticoid receptors and a decrease in glucocorticoid receptor expression levels in the ovary. A decline in FSH receptor expression across stages was also observed in the ovary. Combined, our data suggest seasonal variation in female's sensitivity to signals of HPG activity and energetic or stress signals. These data provide additional insight into the physiological mechanisms regulating onset of clutch initiation.

Early-breeding females experience greater telomere loss.

Annual reproductive success is often highest in individuals that initiate breeding early, yet relatively few individuals start breeding during this apparently optimal time. This suggests that individuals, particularly females who ultimately dictate when offspring are born, incur costs by initiating reproduction early in the season. We hypothesized that increases in the ageing rate of somatic cells may be one such cost. Telomeres, the repetitive DNA sequences on the ends of chromosomes, may be good proxies of biological wear and tear as they shorten with age and in response to stress. Using historical data from a long-term study population of dark-eyed juncos (Junco hyemalis), we found that telomere loss between years was greater in earlier breeding females, regardless of chronological age. There was no relationship between telomere loss and the annual number of eggs laid or chicks that reached independence. However, telomere loss was greater when temperatures were cooler, and cooler temperatures generally occur early in the season. This suggests that environmental conditions could be the primary cause of accelerated telomere loss in early breeders.

Seasonally sympatric but allochronic: differential expression of hypothalamic genes in a songbird during gonadal development.

Allochrony, the mismatch of reproductive schedules, is one mechanism that can mediate sympatric speciation and diversification. In songbirds, the transition into breeding condition and gonadal growth is regulated by the hypothalamic-pituitary-gonadal (HPG) axis at multiple levels. We investigated whether the difference in reproductive timing between two seasonally sympatric subspecies of dark-eyed juncos (Junco hyemalis) was related to gene expression along the HPG axis. During the sympatric pre-breeding stage, we measured hypothalamic and testicular mRNA expression of candidate genes via qPCR in captive male juncos. For hypothalamic mRNA, we found our earlier breeding subspecies had increased expression of gonadotropin-releasing hormone (GnRH) and decreased expression of androgen receptor, oestrogen receptor alpha and mineralocorticoid receptor (MR). Subspecies did not differ in expression of hypothalamic gonadotropin-inhibitory hormone (GnIH) and glucocorticoid receptor (GR). While our earlier breeding subspecies had higher mRNA expression of testicular GR, subspecies did not differ in testicular luteinizing hormone receptor, follicle-stimulating hormone receptor or MR mRNA expression levels. Our findings indicate increased GnRH production and decreased hypothalamic sensitivity to sex steroid negative feedback as factors promoting differences in the timing of gonadal recrudescence between recently diverged populations. Differential gene expression along the HPG axis may facilitate species diversification under seasonal sympatry.

Chronological and Biological Age Predict Seasonal Reproductive Timing: An Investigation of Clutch Initiation and Telomeres in Birds of Known Age.

Female vertebrates that breed earlier in the season generally have greater reproductive success. However, evidence suggests that breeding early may be costly, thus leading to the prediction that females with fewer future reproductive events will breed earlier in the season. While chronological age is a good indicator of remaining life span, telomere lengths may also be good biomarkers of longevity as they potentially reflect lifetime wear and tear (i.e., biological age). We examined whether variation in the timing of the first seasonal clutch was related to age and telomere length in female dark-eyed juncos (Junco hyemalis), predicting that older females and those with shorter telomeres would breed earlier. Both predictions held true and were independent of each other, as telomere length did not significantly vary with age. These results suggest that females may adjust their reproductive effort based on both chronological and biological age.

Postnatal Development of the Degu (Octodon degus) Endocrine Stress Response Is Affected by Maternal Care.

Maternal stress and care significantly affect offspring's future behavior and physiology. Studies in laboratory rats have shown that maternal stress decreases maternal care and that low rates of certain maternal behaviors cause offspring to develop hyperreactive stress responses. Plurally breeding rodents that practice communal care, such as degus (Octodon degus), may be able to buffer some of these effects since offspring receive care from multiple females. Directly after parturition, 0% (Control group), 50% (Mixed group), or 100% (CORT group) per cage of pair-housed female degus were implanted with 21-day release cortisol pellets. The amount of maternal care provided by females was determined from video recordings during the next 3 weeks. Females with cortisol implants did not alter rates of maternal care. However, females recently introduced to captivity had low rates of pup contact and pup retrievals compared to females of captive origin. When pups reached 4 weeks of age, we determined their baseline and stress-induced cortisol levels, in addition to assessing their negative feedback efficacy and adrenal sensitivity. Pups from mothers recently introduced to captivity had weak negative feedback. Within captive pups, those from CORT mothers weighed less compared to pups from either Control or Mixed mothers. Captive CORT pups also had weak adrenal sensitivity compared to captive Control pups. These findings demonstrate that maternal care and glucocorticoid elevation impact certain components of the degu pup stress response, but that plural breeding with communal care may buffer some of these effects.

Hypothalamic-pituitary-adrenal axis activity is not elevated in a songbird (Junco hyemalis) preparing for migration.

During spring, increasing daylengths stimulate gonadal development in migratory birds. However, late-stage reproductive development is typically postponed until migration has been completed. The hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids, which have been associated with pre-migratory hyperphagia and fattening. The HPA-axis is also known to suppress the hypothalamic-pituitary-gonadal (HPG) axis, suggesting the possibility that final transition into the breeding life history stage may be slowed by glucocorticoids. We hypothesized that greater HPA-axis activity in individuals preparing for migration may foster preparation for migration while simultaneously acting as a "brake" on the development of the HPG-axis. To test this hypothesis, we sampled baseline corticosterone (CORT), stress-induced CORT, and negative feedback efficacy of Dark-eyed Juncos (Junco hyemalis) in an overwintering population that included both migratory (J.h. hyemalis) and resident (J.h. carolinensis) individuals. We predicted that compared to residents, migrants would have higher baseline CORT, higher stress-induced CORT, and weaker negative feedback. Juncos were sampled in western Virginia in early March, which was about 2-4wk before migratory departure for migrants and 4-5wk before first clutch initiation for residents. Contrary to our predictions, we found that migrants had lower baseline and stress-induced CORT and similar negative feedback efficacy compared with residents, which suggests that delayed breeding in migrants is influenced by other physiological mechanisms. Our findings also suggest that baseline CORT is not elevated during pre-migratory fattening, as migrants had lower baseline CORT and were fatter than residents.

Maternal stress and plural breeding with communal care affect development of the endocrine stress response in a wild rodent.

Maternal stress can significantly affect offspring fitness. In laboratory rodents, chronically stressed mothers provide poor maternal care, resulting in pups with hyperactive stress responses. These hyperactive stress responses are characterized by high glucocorticoid levels in response to stressors plus poor negative feedback, which can ultimately lead to decreased fitness. In degus (Octodon degus) and other plural breeding rodents that exhibit communal care, however, maternal care from multiple females may buffer the negative impact on pups born to less parental mothers. We used wild, free-living degus to test this hypothesis. After parturition, we manipulated maternal stress by implanting cortisol pellets in 0%, 50-75%, or 100% of adult females within each social group. We then sampled pups for baseline and stress-induced cortisol, negative feedback efficacy, and adrenal sensitivity. From groups where all mothers were implanted with cortisol, pups had lower baseline cortisol levels and male pups additionally had weaker negative feedback compared to 0% or 50-75% implanted groups. Contrary to expectations, stress-induced cortisol did not differ between treatment groups. These data suggest that maternal stress impacts some aspects of the pup stress response, potentially through decreased maternal care, but that presence of unstressed mothers may mitigate some of these effects. Therefore, one benefit of plural breeding with communal care may be to buffer post-natal stress.

Seasonal variation in the degu (Octodon degus) endocrine stress response.

Many wild animals show seasonal variation in circulating levels of stress hormones. Seasonal changes in the stress response may help animals better cope with the different challenges faced during each life history stage. We determined the seasonal stress profile of wild, free-living degus in Chile. Female degus were sampled during non-breeding (January), mating/early gestation (July), late gestation (August), and lactation (1st litter-September, 2nd litter-January). Male degus were sampled during the first three time-points. We measured baseline cortisol (CORT), stress-induced CORT, and negative feedback efficacy using a dexamethasone suppression test. While we found that neither males nor females showed seasonal variation in baseline CORT or negative feedback levels, we did find significant seasonal variation in stress-induced CORT levels of both sexes. Male stress-induced CORT was lowest during mating while female stress-induced CORT was highest during late gestation and lactation. Overall, females had higher stress-induced CORT compared to males. Our data suggest that stress-induced levels of CORT are highest during periods with increased chance of stressor exposure or times of positive energy balance. Consequently, CORT responses to stress appear to be regulated according to different life history needs.

Habitat type influences endocrine stress response in the degu (Octodon degus).

While many studies have examined whether the stress response differs between habitats, few studies have examined this within a single population. This study tested whether habitat differences, both within-populations and between-populations, relate to differences in the endocrine stress response in wild, free-living degus (Octodon degus). Baseline cortisol (CORT), stress-induced CORT, and negative feedback efficacy were measured in male and female degus from two sites and three habitats within one site during the mating/early gestation period. Higher quality cover and lower ectoparasite loads were associated with lower baseline CORT concentrations. In contrast, higher stress-induced CORT but stronger negative feedback efficacy were associated with areas containing higher quality forage. Stress-induced CORT and body mass were positively correlated in female but not male degus across all habitats. Female degus had significantly higher stress-induced CORT levels compared to males. Baseline CORT was not correlated with temperature at time of capture and only weakly correlated with rainfall. Results suggest that degus in habitats with good cover quality, low ectoparasite loads, and increased food availability have decreased endocrine stress responses.

Pharmacological characterization of intracellular glucocorticoid receptors in nine tissues from house sparrow (Passer domesticus).

Glucocorticoid hormones play a key role in the stress response, but plasma concentrations vary based on physiological, environmental, or social parameters. However, hormone titers alone do not determine organismal response. To enhance our understanding of glucocorticoid actions we can examine 'downstream' factors in the organismal stress response, measuring glucocorticoid receptors across target tissues. Here, we characterized intracellular binding sites for CORT (corticosterone, the avian glucocorticoid) in house sparrow (Passer domesticus) brain, liver, skeletal muscle, spleen, fat, testes, ovary, kidney and skin. We used radioligand binding assays to identify total capacity, relative density and affinity for CORT of intracellular receptors in each tissue. Most evidence supported two binding sites similar to mammalian low-affinity glucocorticoid receptor (GR) and a high-affinity mineralocorticoid receptor (MR) for brain, liver, kidney and testes, and only a GR-like receptor for muscle, spleen, fat, ovary and skin. However, kidney data were somewhat more complicated, possibly hinting at a mineralocorticoid function for CORT and/or GR in birds. In all tissues, GR and MR affinities were close to published house sparrow values (K(d)~6 nM for GR, and ~0.2 nM for MR). Taken together, these data show that CORT receptor distribution appears to be as widespread in birds as it is in mammals, and suggest that independent regulation of peripheral receptors in different target tissues may play a role in CORT's diverse physiological effects.

Hypothalamus-pituitary-adrenal axis activity and the subsequent response to chronic stress differ depending upon life history stage.

The hypothalamus-pituitary-adrenal (HPA) axis is modulated seasonally in many species, and chronic stress can alter HPA functioning. However, it is not known how these two factors interact - are there particular life history stages when animals are more or less vulnerable to chronic stress? We captured wild house sparrows (Passer domesticus) in Massachusetts during six different life history stages: early and late winter, pre-laying, breeding, late breeding, and molt. At each time point, we tested HPA function by measuring baseline and stress-induced corticosterone (CORT), negative feedback in response to an injection of dexamethasone, and maximum adrenal response through an injection of adrenocorticotropic hormone. We then brought birds into captivity as a model for chronic stress, and repeated the four tests 5 days later. At capture, all HPA variables varied seasonally. Birds showed increased negative feedback during breeding and late winter compared to pre-laying. Furthermore, birds during the late breeding period had down-regulated their HPA axis, perhaps in preparation for molt. After 5 days of captivity, house sparrows lost ∼11% of initial body mass, although birds lost more weight during molt and early winter. Overall, captive sparrows showed elevated baseline CORT and increased negative feedback, although negative feedback did not show a significant increase during any individual life history stage. During most of the year, adrenal sensitivity was unaffected by captivity. However, during late breeding and molt, adrenal sensitivity increased during captivity. Taken together, these data provide further support that HPA function naturally varies throughout the year, with the interesting consequence that molting birds may potentially be more vulnerable to a chronic stressor such as captivity.