Endocrine responses to environmental variation

Abstract

Hormones regulate most physiological functions and life history from embryonic development to reproduction. In addition to their roles in growth and development, hormones also mediate responses to the abiotic, social and nutritional environments. Hormone signalling is responsive to environmental changes to adjust phenotypes to prevailing conditions. Both hormone levels and receptor densities can change to provide a flexible system of regulation. Endocrine flexibility connects the environment to organismal function, and it is central to understanding environmental impacts and their effect on individuals and populations. Hormones may also act as a ‘sensor’ to link environmental signals to epigenetic processes and thereby effect phenotypic plasticity within and across generations. Many environmental parameters are now changing in unprecedented ways as a result of human activity. The knowledge base of organism–environmental interactions was established in environments that differ in many ways from current conditions as a result of ongoing human impacts. It is an urgent contemporary challenge to understand how evolved endocrine responses will modulate phenotypes in response to anthropogenic environmental impacts including climate change, light-at-night and chemical pollution. Endocrine responses play a central role in ecology, and their integration into conservation can lead to more effective outcomes.

This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.

1. Introduction

Endocrine signalling regulates almost all biological processes, and the action of many hormones is closely linked to environmental signals. Hormones are therefore at the core of animal responses to environmental variation [1]. Endocrine systems are relevant ecologically through integrating environmental signals with fundamental biological responses that underpin individual fitness and the function of ecosystems [2–4]. Most hormones evolved to be multi-functional so that their effects on phenotypes can influence a broad range of ecological functions. Endocrine responses to environmental variability are inherently complex, requiring multidisciplinary research extending from molecular endocrinology to ecology and evolution [5]. For example, thyroid hormones regulate development and metamorphosis in amphibians and teleost fish, metabolic processes, and align physiological responses to seasonal environmental change [6]. Thyroid hormones may also act as environmental sensors to mediate plastic responses via DNA methylation [7]. Similarly, the hypothalamus–pituitary–adrenal (renal) axis and glucocorticoid signalling mediate metabolic responses to changes in the abiotic environment and can prepare an organism to respond to short-term biotic and abiotic stressors [8]. Glucocorticoids have featured prominently in research as biomarkers to assess acute and chronic stress responses [9]. A range of other hormones regulate various biological functions to match animal responses to environmental conditions. For example, leptin and gonadotropins regulate feeding and reproduction, respectively [10–12], and melatonin elicits a cascade of molecular responses to entrain a circadian sleep–wake cycle in response to light stimuli, which can even influence central thyroid processing ([13–15]; figure 1).

Figure 1.

Schematic summary of the Theme Issue. Endocrine responses are dynamic and include context-dependent changes in the levels of circulating hormone and in hormone receptor densities. The resultant endocrine flexibility adjusts phenotypes directly or by inducing epigenetic modifications to match natural variation and rhythms. Anthropogenic impacts including pollution, artificial light-at-night and climate change can disrupt endocrine signalling to the detriment of organismal performance. (All images by the authors; some images were created with AI.)

Anthropogenic endocrine disruption modifies endocrine-mediated responses to natural variation and links the fields of environmental science and toxicology to ecology and conservation biology [16,17]. Understanding of how anthropogenic impacts such as climate change, artificial light-at-night (ALAN) and endocrine disrupting chemicals (EDCs) alter evolved responses of animals is only now emerging [18]. There needs to be a collaborative effort to understand their impacts on non-human animals in the context of their natural and urbanized environments. The ultimate effects of natural and anthropogenic environmental variation (and disruption) on endocrine function are likely to determine the success of populations and species, so that understanding endocrine signalling and flexibility is important for effective conservation [19].

Here we briefly review endocrine responses to environmental variation, including measuring endocrine responses, endocrine flexibility and anthropogenic impacts on endocrine systems. Our mini-review serves to introduce the main themes of this Theme Issue.

2. How to measure endocrine responses?

There are different approaches to analysing hormone signalling, ranging from measures of circulating concentrations in the whole animal to analysing hormone receptor dynamics in local tissues [3,20]. Measuring circulating levels of hormones is relatively simple logistically, and samples can be taken from animals in the wild [21,22]. However, there is not always a clear correspondence between hormone concentrations and hormone signalling, because the latter may depend on receptor characteristics and densities rather than on circulating hormone levels alone [3,23]. Nuclear receptors such as thyroid and glucocorticoid receptors, in particular, are important in transducing endocrine signals by altering gene expression patterns [20,24,25]. It is essential therefore to develop frameworks to interpret hormone responses, and to establish the current state-of-knowledge of the link between various endocrine measures and animal function. For example, circulating glucocorticoid levels are commonly used to assess animal responses to challenging environments. However, glucocorticoid regulatory capacity depends on the interaction between circulating hormone and glucocorticoid receptor density [26]. The relationship between hormone levels and receptor densities can be predicted by a theoretical model tested against empirical data [26]. The model shows that individuals with higher glucocorticoid receptor densities had stronger physiological responses, and greater capacity to adjust physiological responses to environmental stressor intensity. Interestingly, variability in receptor density between individuals masked the correspondence between plasma glucocorticoid levels and physiological responses [26], indicating that plasma levels alone may be an insufficient indicator of stress responses. Ultimately, the crucial aspect of glucocorticoid signalling is its capacity to respond to and compensate for sudden changes in the environment [27], and this capacity is not necessarily reflected in isolated measures of circulating hormone levels. An alternative to measuring circulating hormone levels is the measurement of FKBP5, a protein in the glucocorticoid receptor complex that regulates receptor function and activity. FKBP5 sets the scope of glucocorticoid responses to environmental stressors [27]. Monitoring FKBP5 may therefore be a more effective way to assess endocrine flexibility and the efficacy of the physiological stress responses in individuals [27].

3. Endocrine flexibility

Global environments are inherently variable, and one of the principal challenges for most if not all organisms is to respond appropriately to environmental change, both with respect to the quality and the magnitude of the response. Environmental change represents a major selection pressure that can drive genetic adaptation. However, many environments are dynamic, and long-term mean changes are accompanied by shorter-term variation [28]. Hence, animals must have the capacity to respond relatively rapidly to external signals. Endocrine signals are the principal mechanisms that enable appropriate responses to dynamic environments, as encapsulated by the concept of endocrine flexibility [29–31]. Endocrine flexibility considers hormones as information carriers, which are deployed to effect within-individual rapid and reversible changes in physiological regulation in response to unpredictable challenges [4,32]. Useful information is contained in context-dependent changes in hormone concentrations coupled with receptor binding sensitivities, and individuals that can obtain the ‘best’ information about stressors will also be capable of mounting the most effective response [4,27].

Interestingly, hormone signalling may be intrinsically linked to epigenetic processes that can have lasting effects on phenotypes during the lifetime of an organism and across generations [33]. Epigenetic effects can have an endocrine dimension [34,35]. Hormone signals may enable epigenetic processes by acting as environmental sensors that transduce information about environmental change to epigenetic modifications such as DNA methylation patterns. Thyroid response elements in the promotor region of the genes coding for the principal enzymes underlying DNA methylation, for example, can link sensing of light and temperature by thyroid hormone to DNA methylation patterns [7]. Hence, endocrine flexibility may comprise information transfer by hormones leading to epigenetic changes of phenotypes in response to environmental variability.

4. Endocrine responses to anthropogenic impacts

The three-way interaction between environmental change, hormones and epigenetic processes can have complex impacts on animal function. Given the complexity of evolved endocrine responses, disruption of hormone signalling is likely to produce unexpected and unpredictable effects [36,37]. Most ecosystems in the world are experiencing unprecedented environmental change as a result of human activity. In addition to climate change, ALAN and endocrine disrupting chemicals (EDCs) are two of the most dominant anthropogenic impacts. All three are currently increasing at an alarming rate [38,39], and all three can impact hormone-mediated signalling [40–42]. Importantly, these anthropogenic drivers can interact and alter qualitatively how animals respond to natural variation: existing knowledge of responses to natural environmental variability may therefore be outdated [37,43,44]. Hence, there is considerable urgency to assess how animal responses are altered in the presence of endocrine disruption to facilitate effective conservation [45].

ALAN disrupts biological clocks, which are evolved time-keeping systems that align physiology with daily or seasonal rhythms in environmental temperature and light [15]. Biological clocks are regulated by melatonin and thyroid hormone, and physiological responses are coordinated via glucocorticoid levels and receptors [15,46–48]. ALAN is increasing globally as a result of increasing urbanisation and human activity [49,50] and its disruption of the endocrine-mediated time-keeping system can have pronounced effects on reproduction, growth and behaviour, and thereby reduce fitness and ecosystem function [51–53]

Similarly, environmental concentrations of EDCs, such as bisphenols derived from plastic waste and manufacture, are increasing at an alarming rate worldwide [18,54,55]. EDCs interact with nuclear receptors such as thyroid and glucocorticoid receptors to activate or block endocrine signals [25,56,57]. EDCs thereby impair essential biological functions across a broad range of taxa [58] and have the potential to disrupt ecosystems, particularly in aquatic environments [18]. Environmental exposures throughout the lifetime define the chemical exposome of an organism [59]. The concept originates from medicine to evaluate environmental impacts on human health but has been extended to the eco-exposome that includes non-human systems [60]. The exposome, or components of it, can impact endocrine systems and thereby phenotypes [61]. Organisms have evolved metabolic pathways to eliminate xenobiotics, but detoxification is relatively non-specific and can cause side effects including break-down of endogenous hormones [16].

Climate change and its associated increases in average temperatures and temperature fluctuations can impact animals directly by temperature-induced impairment of physiological rate functions, and of reproductive function and fitness [62]. Endocrine flexibility has the potential to alleviate the negative effects of warming and increased variability, in particular via glucocorticoid signalling [17]. However, there are likely to be taxonomic differences and limits in its efficacy to respond to extreme environments such as urban heat islands. Future research should be directed to increase understanding of the endocrine mechanisms that allow animals to cope with variable conditions, which will help identify the populations that are most vulnerable to climate change [17]. Interestingly, an analysis of glucocorticoid concentrations in 51 species of birds in the USA showed a landscape-level association between stress-induced levels of glucocorticoids and usable land cover within and across species [63]. These data indicate that glucocorticoid levels may be a useful biomarker to characterize populations across their range of available habitats, which can feed into informing conservation strategies. Climate change and increasing temperatures can also interact with endocrine signalling to alter body size and shape [64]. Additionally, warming can exacerbate the effects of EDCs [43] and intensify their negative impact on size, growth and metabolism [65]. These compounded effects could disrupt energy transfer between trophic levels and should be incorporated into population models such as fisheries models [66].

Endocrine signalling is an essential mechanism by which organisms respond to environmental change and potentially alleviate its negative effects. Endocrine responses are therefore an essential component in evolution, ecology and conservation. In the face of rapidly changing global environments, conservation efforts can only achieve a fraction of their effectiveness if endocrine responses are not incorporated explicitly.

Data accessibility

This article has no additional data.

Declaration of AI use

We have used AI-assisted technologies in creating this article.

Authors' contributions

A.G.L.: conceptualization, writing—review and editing; F.S.: conceptualization, writing—original draft, writing—review and editing.

Both authors gave final approval for publication and agreed to be held accountable for the work performed therein.

Conflict of interest declaration

We declare we have no competing interests.

Funding

F.S. and A.G.L. were supported by Australian Research Council Discovery Grant DP220101342, and A.G.L. was supported by a Natural Sciences and Engineering Council of Canada (NSERC) Discovery Grant (grant no. DGECR 2021-00123) and Alliance Collaboration Grant (grant no. ALLRP 571888-21).