A multi-tissue metabolome atlas of primate pregnancy.

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.

Monocytes re-enter the bone marrow during fasting and alter the host response to infection.

Diet profoundly influences physiology. Whereas over-nutrition elevates risk for disease via its influence on immunity and metabolism, caloric restriction and fasting appear to be salutogenic. Despite multiple correlations observed between diet and health, the underlying biology remains unclear. Here, we identified a fasting-induced switch in leukocyte migration that prolongs monocyte lifespan and alters susceptibility to disease in mice. We show that fasting during the active phase induced the rapid return of monocytes from the blood to the bone marrow. Monocyte re-entry was orchestrated by hypothalamic-pituitary-adrenal (HPA) axis-dependent release of corticosterone, which augmented the CXCR4 chemokine receptor. Although the marrow is a safe haven for monocytes during nutrient scarcity, re-feeding prompted mobilization culminating in monocytosis of chronologically older and transcriptionally distinct monocytes. These shifts altered response to infection. Our study shows that diet-in particular, a diet's temporal dynamic balance-modulates monocyte lifespan with consequences for adaptation to external stressors.

Activity in a prefrontal-periaqueductal gray circuit overcomes behavioral and endocrine features of the passive coping stress response.

The question of how the brain links behavioral and biological features of defensive responses has remained elusive. The importance of this problem is underscored by the observation that behavioral passivity in stress coping is associated with elevations in glucocorticoid hormones, and each may carry risks for susceptibility to a host of stress-related diseases. Past work implicates the medial prefrontal cortex (mPFC) in the top-down regulation of stress-related behaviors; however, it is unknown whether such changes have the capacity to buffer against the longer-lasting biological consequences associated with aversive experiences. Using the shock probe defensive burying test in rats to naturalistically measure behavioral and endocrine features of coping, we observed that the active behavioral component of stress coping is associated with increases in activity along a circuit involving the caudal mPFC and midbrain dorsolateral periaqueductal gray (PAG). Optogenetic manipulations of the caudal mPFC-to-dorsolateral PAG pathway bidirectionally modulated active (escape and defensive burying) behaviors, distinct from a rostral mPFC-ventrolateral PAG circuit that instead limited passive (immobility) behavior. Strikingly, under conditions that biased rats toward a passive coping response set, including exaggerated stress hormonal output and increased immobility, excitation of the caudal mPFC-dorsolateral PAG projection significantly attenuated each of these features. These results lend insight into how the brain coordinates response features to overcome passive coping and may be of importance for understanding how activated neural systems promote stress resilience.

Cortical-brainstem circuitry attenuates physiological stress reactivity.

Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycaemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC-RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC-RVLM circuit utilizing genetically encoded anterograde and retrograde tract tracers. Together, these studies found that stress-activated vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC-RVLM circuit during restraint stress suppressed glycaemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behaviour in either sex. Further analysis indicated that circuit stimulation preferentially activated non-catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely by recruiting local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity and stress-related health outcomes. KEY POINTS: Glutamatergic efferents from the ventromedial prefrontal cortex target catecholaminergic neurons throughout the ventrolateral medulla. Partially segregated, stress-activated ventromedial prefrontal cortex populations innervate the rostral and caudal ventrolateral medulla. Stimulating ventromedial prefrontal cortex synapses in the rostral ventrolateral medulla decreases stress-induced glucocorticoid release in males and females. Stimulating ventromedial prefrontal cortex terminals in the rostral ventrolateral medulla preferentially activates non-catecholaminergic neurons. Ventromedial prefrontal cortex terminals target medullary inhibitory neurons.

Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control.

Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in postnatal liver as a potential major RA catabolizing enzyme and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 contributes only marginally to endogenous RA homeostasis postnatally. We report reevaluation of a conditional Cyp26a1 knockdown in the postnatal mouse. The current results show that Cyp26a1 mRNA in WT mouse liver increases 16-fold upon refeeding after a fast, accompanied by an increased rate of RA elimination and a 41% decrease in the RA concentration. In contrast, Cyp26a1 mRNA in the refed homozygotic knockdown reached only 2% of its extent in WT during refeeding, accompanied by a slower rate of RA catabolism and no decrease in liver RA, relative to fasting. Refed homozygous knockdown mice also had decreased Akt1 and 2 phosphorylation and pyruvate dehydrogenase kinase 4 (Pdk4) mRNA and increased glucokinase (Gck) mRNA, glycogen phosphorylase (Pygl) phosphorylation, and serum glucose, relative to WT. Fasted homozygous knockdown mice had increased glucagon/insulin relative to WT. These data indicate that Cyp26a1 participates prominently in moderating the postnatal liver concentration of endogenous RA and contributes essentially to glucoregulatory control.

TRPV1 and mast cell involvement in repeated variate stress-induced urinary bladder dysfunction in adult female mice.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. Transient receptor potential vanilloid 1 (TRPV1) channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (P ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild-type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell-deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression, whereas control (no stress) mast cell-deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia (DRG) in WT mice exposed to RVS, but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.NEW & NOTEWORTHY Using pharmacological tools and transgenic mice in a repeated variate stress (RVS) model in female mice, we demonstrate that transient receptor potential vanilloid 1 (TRPV1) and mast cells contribute to the increased voiding frequency observed following RVS. TRPV1 and mast cells should continue to be considered as targets to improve bladder function in stress-induced bladder dysfunction.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra-PVN injection of ODQ did not alter the number of Fos-immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint-induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC-mediated signalling in the PVN plays a key role in acute stress-induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint-evoked hypothalamus-pituitary-adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.

Angiotensinergic effect of ß-Caryophyllene on Lipopolysaccharide- induced systemic inflammation.

Renin-Angiotensin System (RAS) is a peptidergic system, canonically known for its role in blood pressure regulation. Furthermore, a non-canonical RAS regulates pathophysiological phenomena, such as inflammation since it consists of two main axes: the pro-inflammatory renin/(pro)renin receptor ((P)RR) axis, and the anti-inflammatory angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1-7) (Ang-(1-7))/Mas Receptor (MasR) axis. Few phytochemicals have shown to exert angiotensinergic and anti-inflammatory effects through some of these axes; nevertheless, anti-inflammatory drugs, such as phytocannabinoids have not been studied regarding this subject. Among phytocannabinoids, ß-Caryophyllene stands out as a dietary phytocannabinoid with antiphlogistic activity that possess a unique sesquiterpenoid structure. Although its cannabinergic effect has been studied, its angiotensinergic effect reminds underexplored. This study aims to explore the angiotensinergic effect of ß-Caryophyllene on inflammation and stress at a systemic level. After intranasal Lipopolysaccharide (LPS) installation and oral treatment with ß-Caryophyllene, the concentration and activity of key RAS elements in the serum, such as Renin, ACE2 and Ang-(1-7), along with the stress hormone corticosterone and pro/anti-inflammatory cytokines, were measured in mice serum. The results show that ß-Caryophyllene treatment modified RAS levels by increasing Renin and Ang-(1-7), alongside the reduction of pro-inflammatory cytokines and corticosterone levels. These results indicate that ß-Caryophyllene exhibits angiotensinergic activity in favor of anti-inflammation.

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant- and anxiolytic-like effects in female rats.

Finasteride is used in female-pattern hair loss, hirsutism, and polycystic ovarian syndrome. It inhibits 5α-reductase, which is an important enzyme in the biosynthesis of neurosteroids. The effects of finasteride treatment on mental health in female patients as well as the effects of repeated/chronic finasteride administration in female rodents are still unknown. Accordingly, in our study, we administered finasteride (10, 30, or 100 mg/Kg, s.c.) for 6 days in female rats and evaluated behavior, plasma steroid levels, and synaptic plasticity. Depression-like behavior was evaluated using forced swim test (FST) and splash test. Anxiety-like behavior was evaluated using novelty-suppressed feeding task (NSFT), elevated plus maze (EPM), open field test (OFT), and light-dark test (LDT). Plasma steroid levels were assessed using ELISA and synaptic plasticity by field potential recordings. We observed that finasteride decreased total immobility duration in FST, indicating antidepressant-like effect and decreased the latency to first bite in NSFT, showing anxiolytic-like effect. We also found a significant increase in plasma estradiol and a significant decrease in plasma corticosterone level. Furthermore, field potential recordings showed that finasteride increased hippocampal long-term potentiation. These results indicate that repeated finasteride administration in female rats may have antidepressant- and anxiolytic-like effect, which might be mediated by enhanced estradiol levels or decreased corticosterone levels. Further studies are required to validate the molecular mechanisms underlying the effects of finasteride in female rats. Understanding the mechanisms will help us in developing novel neurosteroid-based therapeutics in the treatment of neuropsychiatric disorders in women.

Feather corticosterone is lower in translocated and historical populations of the endangered Laysan duck (Anas laysanensis).

Identifying reliable bioindicators of population status is a central goal of conservation physiology. Physiological stress measures are often used as metrics of individual health and can assist in managing endangered species if linked to fitness traits. We analysed feather corticosterone, a cumulative physiological stress metric, of individuals from historical, translocated, and source populations of an endangered endemic Hawaiian bird, the Laysan duck (Anas laysanensis). We hypothesized that feather corticosterone would reflect the improved reproduction and survival rates observed in populations translocated to Midway and Kure Atolls from Laysan Island. We also predicted less physiological stress in historical Laysan birds collected before ecological conditions deteriorated and the population bottleneck. All hypotheses were supported: we found lower feather corticosterone in the translocated populations and historical samples than in those from recent Laysan samples. This suggests that current Laysan birds are experiencing greater physiological stress than historical Laysan and recently translocated birds. Our initial analysis suggests that feather corticosterone may be an indicator of population status and could be used as a non-invasive physiological monitoring tool for this species with further validation. Furthermore, these preliminary results, combined with published demographic data, suggest that current Laysan conditions may not be optimal for this species.

The microbiome at the interface between environmental stress and animal health: an example from the most threatened vertebrate group.

Nitrate pollution and global warming are ubiquitous stressors likely to interact and affect the health and survival of wildlife, particularly aquatic ectotherms. Animal health is largely influenced by its microbiome (commensal/symbiotic microorganisms), which responds to such stressors. We used a crossed experimental design including three nitrate levels and five temperature regimes to investigate their interactive and individual effects on an aquatic ectotherm, the European common frog. We associated health biomarkers in larvae with changes in gut bacteria diversity and composition. Larvae experienced higher stress levels and lower body condition under high temperatures and nitrate exposure. Developmental rate increased with temperature but decreased with nitrate pollution. Alterations in bacteria composition but not diversity are likely to correlate with the observed outcomes in larvae health. Leucine degradation decreased at higher temperatures corroborating accelerated development, nitrate degradation increased with nitrate level corroborating reduced body condition and an increase in lysine biosynthesis may have helped larvae deal with the combined effects of both stressors. These results reinforce the importance of associating traditional health biomarkers with underlying microbiome changes. Therefore, we urge studies to investigate the effects of environmental stressors on microbiome composition and consequences for host health in a world threatened by biodiversity loss.

Effects of the combination of chronic unpredictable stress and environmental enrichment on anxiety-like behavior assessed using the elevated plus maze in Swiss male mice: Hypothalamus-Pituitary-Adrenal Axis-mediated mechanisms.

Environmental enrichment (EE) is a paradigm that offers the animal a plethora of stimuli, including physical, cognitive, sensory, and social enrichment. Exposure to EE can modulate both anxiety responses and plasma corticosterone. In this study, our objective was to explore how chronic unpredictable stress (CUS) impacts anxiety-related behaviors in male Swiss mice raised in EE conditions. Additionally, we investigated corticosterone and adrenocorticotropic hormone (ACTH) levels to assess the involvement of the hypothalamic-pituitary-adrenal (HPA) axis in mediating these responses. Mice were housed under either EE or standard housing conditions for 21 days. Afterward, they were exposed to 11 days of CUS while still reared in their distinct housing conditions, with half of the mice receiving daily pretreatment with the vehicle and the other half receiving daily metyrapone (MET) injections, an inhibitor of steroid synthesis, 30 mins before CUS exposure. Blood samples were obtained to assess plasma corticosterone and ACTH levels. The 11-day CUS protocol induced anxiety-like phenotype and elevated ACTH levels in EE mice. Chronic MET pretreatment prevented anxiety-like behavior in the EE-CUS groups, by mechanisms involving increased plasma corticosterone levels and decreased ACTH. These results suggest a role of the HPA axis in the mechanism underlying the anxiogenic phenotype induced by CUS in EE mice and shed light on the complex interplay between environmental factors, stress, and the HPA axis in anxiety regulation.

The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior in rats is dependent on sex and vendor.

Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Treatment naïve male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior.

Corticosterone disrupts spatial working memory during retention testing when highly taxed, which positively correlates with depressive-like behavior in middle-aged, ovariectomized female rats.

Major Depressive Disorder affects 8.4 % of the U.S. population, particularly women during perimenopause. This study implemented a chronic corticosterone manipulation (CORT, a major rodent stress hormone) using middle-aged, ovariectomized female rats to investigate depressive-like behavior, anxiety-like symptoms, and cognitive ability. CORT (400 µg/ml, in drinking water) was administered for four weeks before behavioral testing began and continued throughout all behavioral assessments. Compared to vehicle-treated rats, CORT significantly intensified depressive-like behaviors: CORT decreased sucrose preference, enhanced immobility on the forced swim test, and decreased sociability on a choice task between a novel conspecific female rat and an inanimate object. Moreover, CORT enhanced anxiety-like behavior on a marble bury task by reducing time investigating tabasco-topped marbles. No effects were observed on novelty suppressed feeding or the elevated plus maze. For spatial working memory using an 8-arm radial arm maze, CORT did not alter acquisition but disrupted performance during retention. CORT enhanced the errors committed during the highest working memory load following a delay and during the last trial requiring the most items to remember; this cognitive metric positively correlated with a composite depressive-like score to reveal that as depressive-like symptoms increased, cognitive performance worsened. This protocol allowed for the inclusion of multiple behavioral assessments without stopping the CORT treatment needed to produce a MDD phenotype and to assess a battery of behaviors. Moreover, that when middle-age was targeted, chronic CORT produced a depressive-like phenotype in ovariectomized females, who also comorbidly expressed aspects of anxiety and cognitive dysfunction.

Early life adversity reduces affiliative behavior with a stressed cagemate and leads to sex-specific alterations in corticosterone responses in adult mice.

Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both groups of mice 20 or 90 min after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.

Experimentally elevated corticosterone does not affect bacteria killing ability of breeding female tree swallows (Tachycineta bicolor).

The immune system can be modulated when organisms are exposed to acute or chronic stressors. Glucocorticoids (GCs), the primary hormonal mediators of the physiological stress response, are suspected to play a crucial role in immune modulation. However, most evidence of stress-associated immunomodulation does not separate the effects of glucocorticoid-dependent pathways from those of glucocorticoid-independent mechanisms on immune function. In this study, we experimentally elevated circulating corticosterone, the main avian glucocorticoid, in free-living female tree swallows (Tachycineta bicolor) for one to two weeks to test its effects on immune modulation. Natural variation in bacteria killing ability (BKA), a measure of innate constitutive immunity, was predicted by the interaction between timing of breeding and corticosterone levels. However, experimental elevation of corticosterone had no effect on BKA. Therefore, even when BKA is correlated with natural variation in glucocorticoid levels, this relationship may not be causal. Experiments are necessary to uncover the causal mechanisms of immunomodulation and the consequences of acute and chronic stress on disease vulnerability. Findings in other species indicate that acute increases in GCs can suppress BKA; but our results support the hypothesis that this effect does not persist over longer timescales, during chronic elevations in GCs. Direct comparisons of the effects of acute vs. chronic elevation of GCs on BKA will be important for testing this hypothesis.

Prolactin is associated with proximity to incubating partner rather than parental care in black-headed gulls.

The peptide hormone prolactin plays an important role in the expression of parental care behaviours across bird and mammal taxa. While a great deal is known about how plasma prolactin concentrations vary across the reproductive cycle, the few studies that investigate how prolactin relates to individual-level variation in parental care have reported mixed results. We argue that, since parental care is also affected by social interactions and environmental constraints, prolactin may better reflect behaviours that are indirectly related to parenting than the absolute level of care that is eventually expressed. In this study, we tested for associations between plasma prolactin and the expression of both parental care and proximity to the partner in incubating black-headed gulls, Chroicocephalus ridibundus. Baseline prolactin levels increased with calendar date but were unrelated to incubation behaviours. However, parents who showed a weaker decrease in prolactin to an acute stressor spent more time in close proximity to their incubating partner while not on the nest themselves, suggesting that individual variation in stress-induced prolactin changes reflect differences in parents' tendency to be closely associated with their partner and the joint nesting attempt. Baseline and stress-induced levels of the stress hormone corticosterone were unrelated to both prolactin levels and parental behaviours, suggesting that this hormone is not a strong moderator of parental care in black-headed gulls. One potential explanation for the link between prolactin dynamics and partner proximity is that prolactin reflects parental motivation to provide parental care or retain contact with the breeding partner, but further work is needed to directly test this hypothesis.

Noise and light pollution elicit endocrine responses in urban but not forest frogs.

Urban areas are characterised by the presence of sensory pollutants, such as anthropogenic noise and artificial light at night (ALAN). Animals can quickly adapt to novel environmental conditions by adjusting their behaviour, which is proximately regulated by endocrine systems. While endocrine responses to sensory pollution have been widely reported, this has not often been linked to changes in behaviour, hampering the understanding of adaptiveness of endocrine responses. Our aim was, therefore, to investigate the effects of urbanisation, specifically urban noise and light pollution, on hormone levels in male urban and forest túngara frogs (Engystomops pustulosus), a species with reported population divergence in behaviour in response to urbanisation. We quantified testosterone and corticosterone release rates in the field and in the lab before and after exposure to urban noise and/or light. We show that urban and forest frogs differ in their endocrine phenotypes under field as well as lab conditions. Moreover, in urban frogs exposure to urban noise and light led, respectively, to an increase in testosterone and decrease in corticosterone, whereas in forest frogs sensory pollutants did not elicit any endocrine response. Our results show that urbanisation, specifically noise and light pollution, can modulate hormone levels in urban and forest populations differentially. The observed endocrine responses are consistent with the observed behavioural changes in urban frogs, providing a proximate explanation for the presumably adaptive behavioural changes in response to urbanisation.

In your CORT: Corticosterone and its receptors in the brain underlie mate choosiness in female Cope's gray treefrogs (Hyla chrysoscelis).

Selecting an attractive mate can involve trade-offs related to investment in sampling effort. Glucocorticoids like corticosterone (CORT) are involved in resolving energetic trade-offs. However, CORT is rarely studied in the context of mate choice, despite its elevated levels during reproductive readiness and the energetic transitions that characterize reproduction. Few systems are as well suited as anuran amphibians to evaluate how females resolve energetic trade-offs during mate choice. Phonotaxis tests provide a robust bioassay of mate choice that permit the precise measurement of inter-individual variation in traits such as choosiness-the willingness to pursue the most attractive mate despite costs. In Cope's gray treefrogs (Hyla chrysoscelis), females exhibit remarkable variation in circulating CORT as well as choosiness during mate choice, and a moderate dose of exogenous CORT rapidly (<1 h) and reliably induce large increases in choosiness. Here we measured the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors in the brains of females previously treated with exogenous CORT and tested for mate choosiness. We report a large decrease in GR expression in the hindbrain and midbrain of females that were treated with the moderate dosage of CORT-the same treatment group that exhibited a dramatic increase in choosiness following CORT treatment. This association, however, does not appear to be causal, as only forebrain GR levels, which are not affected by CORT injection, are positively associated with variation in choosiness. No strong effects were found for MR. We discuss these findings and suggest future studies to test the influence of glucocorticoids on mate choice.

Early life conditions reduce similarity between reproductive partners in HPA axis response to stress.

Social environments modulate endocrine function, yet it is unclear whether individuals can become like their social partners in how they physiologically respond to stressors. This social transmission of hypothalamic-pituitary-adrenal (HPA) axis reactivity could have long-term consequences for health and lifespan of individuals if their social partners react to stressors with an exaggerated HPA axis response. We tested whether glucocorticoid levels in response to stress of breeding partners changes after breeding depending on whether partners had similar or dissimilar postnatal conditions. We manipulated postnatal conditions by mimicking early life stress in zebra finch chicks (Taeniopygia guttata) via postnatal corticosterone exposure. When they reached adulthood, we created breeding pairs where the female and male had experienced either the same or different early life hormonal treatment (corticosterone or control). Before and after breeding, we obtained blood samples within 3 min and after 10 min or 30 min of restraint stress (baseline, cort10, cort30). We found that corticosterone levels of individuals in response to restraint were affected by their own and their partner's early life conditions, but did not change after breeding. However, across all pairs, partners became more similar in cort30 levels after breeding, although differences between partners in cort10 remained greater in pairs with a corticosterone-treated female. Thus, we show that HPA axis response to stressors in adulthood can be modulated by reproductive partners and that similarity between partners is reduced when females are postnatally exposed to elevated glucocorticoids.