Glucocorticoid and adrenergic receptor distribution across human organs and tissues: a map for stress transduction

Abstract

Abstract Objective Psychosocial stress is transduced into disease risk through energy-dependent release of hormones from the HPA and SAM axes. The levels of glucocorticoid and adrenergic hormones, together with the sensitivity of tissues to their signaling, define stress responses. To understand existing pathways responsible for the psychobiological transduction of stressful experiences, we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor expression. Methods We systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and β-adrenergic receptors (AR-α1B, AR-α2B AR-β2, and AR-β3), across 55 different organs using the Human Protein Atlas dataset. Given that mitochondria produce the energy required to respond to stress, we leveraged the Human Proteome Map and MitoCarta3.0 data to examine the link between stress hormone receptor density and mitochondrial gene expression. Finally, we tested the functional interplay between GR activation and AR expression in human fibroblast cells. Results The GR was expressed ubiquitously across all investigated organ systems, while AR subtypes showed lower and more localized expression patterns. Receptor co-regulation, meaning the correlated gene expression of multiple stress hormone receptors, was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In cultured human fibroblasts, activating the GR selectively increased AR-β2 and AR-α1B expression. Consistent with the known energetic cost of stress responses, GR and AR expression were positively associated with the expression of specific mitochondrial pathways. Conclusion Our results provide a cartography of GR and AR expression across the human body. Because stress-induced GR and AR signaling trigger energetically expensive cellular pathways involving energy-transforming mitochondria, the tissue-specific expression and co-expression patterns of hormone receptor subtypes may in part determine the resilience or vulnerability of different organ systems.