An official website of the United States government
Hypothalamic–pituitary–adrenal axis (HPA) flexibility is an emerging concept recognizing that individuals that will cope best with stressors will probably be those using their hormones in the most adaptive way. The HPA flexibility concept considers glucocorticoids as molecules that convey information about the environment from the brain to the body so that the organismal phenotype comes to complement prevailing conditions. In this context, FKBP5 protein appears to set the extent to which circulating glucocorticoid concentrations can vary within and across stressors. Thus,FKBP5expression, and the HPA flexibility it causes, seem to represent an individual's ability to regulate its hormones to orchestrate organismal responses to stressors. AsFKBP5expression can also be easily measured in blood, it could be a worthy target of conservation-oriented research attention. We first review the known and likely roles of HPA flexibility and FKBP5 in wildlife. We then describe putative genetic, environmental and epigenetic causes of variation in HPA flexibility andFKBP5expression among and within individuals. Finally, we hypothesize how HPA flexibility andFKBP5expression should affect organismal fitness and hence population viability in response to human-induced rapid environmental changes, particularly urbanization. This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
more »
« less
FKBP5 : A Key Mediator of How Vertebrates Flexibly Cope with Adversity
Abstract Flexibility in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis is an important mediator of stress resilience as it helps organisms adjust to, avoid, or compensate for acute and chronic challenges across changing environmental contexts. Glucocorticoids remain the favorite metric from medicine to conservation biology to attempt to quantify stress resilience despite the skepticism around their consistency in relation to individual health, welfare, and fitness. We suggest that a cochaperone molecule related to heat shock proteins and involved in glucocorticoid receptor activity, FKBP5, may mediate HPA flexibility and therefore stress resilience because it affects how individuals can regulate glucocorticoids and therefore capacitates their abilities to adjust phenotypes appropriately to prevailing, adverse conditions. Although the molecule is well studied in the biomedical literature, FKBP5 research in wild vertebrates is limited. In the present article, we highlight the potential major role of FKBP5 as mediator of HPA axis flexibility in response to adversity in humans and lab rodents.
more »
« less
- Award ID(s):
- 2027040
- PAR ID:
- 10283085
- Date Published:
- Journal Name:
- BioScience
- Volume:
- 70
- Issue:
- 12
- ISSN:
- 0006-3568
- Page Range / eLocation ID:
- 1127 to 1138
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Stress resilience is defined as the ability to rebound to a homeostatic state after exposure to a perturbation. Organisms modulate various physiological mediators to respond to unpredictable changes in their environment. The gut microbiome is a key example of a physiological mediator that coordinates a myriad of host functions including counteracting stressors. Here, we highlight the gut microbiome as a mediator of host stress resilience in the framework of the reactive scope model. The reactive scope model integrates physiological mediators with unpredictable environmental changes to predict how animals respond to stressors. We provide examples of how the gut microbiome responds to stressors within the four ranges of the reactive scope model (i.e., predictive homeostasis, reactive homeostasis, homeostatic overload, and homeostatic failure). We identify measurable metrics of the gut microbiome that could be used to infer the degree to which the host is experiencing chronic stress, including microbial diversity, flexibility, and gene richness. The goal of this perspective piece is to highlight the underutilized potential of measuring the gut microbiome as a mediator of stress resilience in wild animal hosts.more » « less
-
ABSTRACT As a response to environmental cues, maternal glucocorticoids (GCs) may trigger adaptive developmental plasticity in the physiology and behavior of offspring. In North American red squirrels (Tamiasciurus hudsonicus), mothers exhibit increased GCs when conspecific density is elevated, and selection favors more aggressive and perhaps more active mothers under these conditions. We tested the hypothesis that elevated maternal GCs cause shifts in offspring behavior that may prepare them for high-density conditions. We experimentally elevated maternal GCs during gestation or early lactation. We measured two behavioral traits (activity and aggression) in weaned offspring using standardized behavioral assays. Because maternal GCs may influence offspring hypothalamic–pituitary–adrenal (HPA) axis dynamics, which may in turn affect behavior, we also measured the impact of our treatments on offspring HPA axis dynamics (adrenal reactivity and negative feedback), and the association between offspring HPA axis dynamics and behavior. Increased maternal GCs during lactation, but not gestation, slightly elevated activity levels in offspring. Offspring aggression and adrenal reactivity did not differ between treatment groups. Male, but not female, offspring from mothers treated with GCs during pregnancy exhibited stronger negative feedback compared with those from control mothers, but there were no differences in negative feedback between lactation treatment groups. Offspring with higher adrenal reactivity from mothers treated during pregnancy (both controls and GC-treated) exhibited lower aggression and activity. These results suggest that maternal GCs during gestation or early lactation alone may not be a sufficient cue to produce substantial changes in behavioral and physiological stress responses in offspring in natural populations.more » « less
-
null (Ed.)ABSTRACT The hypothalamic–pituitary–adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days. We collected blood at baseline, 2 h and 4 days after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2 h, with effects diminishing at 4 days. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4 days. ACTH decreased neutrophils at 2 h, while decreasing lymphocytes and increasing the neutrophil:lymphocyte ratio at 4 days. These effects were abolished by RU486. Despite alterations in white blood cells, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4 day fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2 h) and chronic (4 days) modulatory effects of HPA activation on white blood cells and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' extraordinary resistance to oxidative stress derived from repeated HPA activation.more » « less
-
Abstract Ongoing amphibian population declines are caused by factors such as climate change, habitat destruction, pollution and infectious diseases not limited to chytridiomycosis. Unfortunately, action is taken against these factors once population collapses are underway. To avoid these post hoc responses, wildlife endocrinology aims to analyse physiological mediators that predict future population declines to inform wildlife management. Mediators typically investigated are stress hormones known as glucocorticoids, which are produced by the Hypothalamus—Pituitary—Interrenal axis (HPI axis). The HPI axis is the part of the endocrine system that helps amphibians cope with stress. Chronic increases in glucocorticoids due to stress can lead to immune dysfunction, which makes amphibians more susceptible to infectious diseases. Despite this predictive potential of glucocorticoids, interpretation of glucocorticoid data is confounded by sampling design and type. Glucocorticoid monitoring classically involves blood sampling, which is not widely applicable in amphibians as some are too small or delicate to sample, and repeated samples are often valued. To address this, we tried to validate skin swabbing via corticosterone (CORT) and adrenocorticotropin hormone (ACTH) injections in adults of two amphibian species: Eastern red-spotted newts, Notophthalmus viridescens viridescens, with natural skin infections with Batrachochytrium dendrobatidis (Bd) upon collection in the field, and Northern leopard frogs, Rana (Lithobates) pipiens, raised in captivity and naïve to Bd exposure. Further, we determined the predictive potential of skin glucocorticoids on Bd load in the field via correlations in Eastern red-spotted newts. We found that hormones present in the skin are not related to the HPI axis and poorly predict infection load; however, skin hormone levels strongly predicted survival in captivity. Although skin swabbing is not a valid method to monitor HPI axis function in these species, the hormones present in the skin still play important roles in organismal physiology under stressful conditions relevant to wildlife managers.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/biosci/biaa114
