Instituto de Investigación en Recursos Cinegéticos (IREC), CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain.
Laboratoire d'Ethologie Expérimentale et Comparée, LEEC, Université Sorbonne Paris Nord, UR 4443, 93430 Villetaneuse, France; Global Health and Infectious Disease Research Center, University of South Florida, 33612 Tampa, FL, USA.
Horm Behav. 2022 Sep;145:105240. doi: 10.1016/j.yhbeh.2022.105240. Epub 2022 Aug 4.
Organisms have to cope with the changes that take place in their environment in order to keep their physical and psychological stability. In vertebrates, the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in mediating phenotypic adjustments to environmental changes, primarily by regulating glucocorticoids (GCs). Although circulating GCs have widely been used as proxy for individual health and fitness, our understanding of HPA regulation is still very limited, especially in free-living animals. Circulating GCs only exert their actions when they are bound to receptors, and therefore, GC receptors play a pivotal role mediating HPA regulation and GC downstream phenotypic changes. Because under challenging conditions GC actions (as well as negative feedback activation) occur mainly through binding to low-affinity glucocorticoid receptors (GR), we propose that GR activity, and in particular GR expression, may play a crucial role in GC regulation and dynamics, and be ultimately related to organismal capacity to appropriately respond to environmental changes. Thus, we suggest that GR expression will provide more comprehensive information of GC variation and function. To support this idea, we compile previous evidence demonstrating the fundamental role of GR on GC responses and the fine-tuning of circulating GCs. We also make predictions about the phenotypic differences in GC responsiveness - and ultimately HPA regulation capacity - associated with differences in GR expression, focusing on GC plasticity and efficiency. Finally, we discuss current priorities and limitations of integrating measures of GR expression into evolutionary endocrinology and ecology studies, and propose further research directions towards the use of GR expression and the study of the mechanisms regulating GR activity to gather information on coping strategies and stress resilience. Our goals are to provide an integrative perspective that will prompt reconsideration on the ecological and physiological interpretation of current GC measurements, and motivate further research on the role of GR in tuning individual responses to dynamic environments.
生物必须应对其环境中发生的变化，以保持其生理和心理稳定。在脊椎动物中，下丘脑-垂体-肾上腺 (HPA) 轴在介导对环境变化的表型调整方面发挥着关键作用，主要通过调节糖皮质激素 (GCs)。尽管循环 GCs 已广泛用作个体健康和适应力的替代指标，但我们对 HPA 调节的理解仍然非常有限，尤其是在自由生活的动物中。只有当与受体结合时，循环 GCs 才会发挥作用，因此，GC 受体在介导 HPA 调节和 GC 下游表型变化方面起着关键作用。由于在具有挑战性的条件下，GC 作用（以及负反馈激活）主要通过与低亲和力糖皮质激素受体 (GR) 结合而发生，我们提出 GR 活性，特别是 GR 表达，可能在 GC 调节和动态中发挥关键作用，并最终与机体适当应对环境变化的能力有关。因此，我们认为 GR 表达将提供更全面的 GC 变化和功能信息。为了支持这一观点，我们汇集了先前的证据，证明了 GR 在 GC 反应和循环 GCs 的微调中的基本作用。我们还对与 GR 表达差异相关的 GC 反应性的表型差异——最终是 HPA 调节能力——做出预测，重点关注 GC 的可塑性和效率。最后，我们讨论了将 GR 表达测量纳入进化内分泌学和生态学研究的当前优先事项和局限性，并提出了进一步研究方向，以研究 GR 表达和调节 GR 活性的机制，以获取关于应对策略和压力恢复力的信息。我们的目标是提供一个综合的视角，促使重新考虑当前 GC 测量的生态和生理学解释，并激励进一步研究 GR 在调节个体对动态环境的反应中的作用。
