Work

Non-Genomic Cortisol Signaling Regulates Early Myogenic Gene Expression in Rainbow Trout Skeletal Muscle

Year: 2025

Type: article

Abstract: Glucocorticoids are key regulators of vertebrate physiology, orchestrating metabolic, immune, and developmental processes that enable adaptation to stress. In teleosts, cortisol is the primary glucocorticoid, acting through classical genomic pathways and rapid non-genomic mechanisms. Although genomic signaling has been widely characterized, non-genomic actions remain poorly understood in skeletal muscle, a tissue of both biological and economic importance. In this study, we examined the effects of cortisol and its membrane-impermeable analog, cortisol-BSA, on rainbow trout (Oncorhynchus mykiss) skeletal muscle under in vivo and in vitro conditions. Transcript analysis demonstrated that cortisol and cortisol-BSA rapidly induced pax3 (2.28 ± 0.22- and 2.48 ± 0.45-fold change, respectively) and myf5 expression (3.03 ± 0.47- and 2.31 ± 0.29-fold change, respectively) at 1 h, whereas prolonged cortisol and cortisol-BSA exposure resulted in their downregulation (0.34 ± 0.07- and 0.38 ± 0.14-fold change, respectively). In cultured myotubes, cortisol-BSA activated protein kinase A (PKA) (2.24 ± 0.25-fold change) and enhanced phosphorylation of its downstream target CREB (3.2 ± 0.21-fold change) in a time-dependent manner; these effects were abolished by the PKA inhibitor H89. Moreover, inhibition of PKA signaling suppressed cortisol-BSA–induced pax3 and myf5 expression (1.31 ± 0.28-fold change and 1.89 ± 0.28-fold change, respectively). Together, these findings provide the first mechanistic evidence that non-genomic cortisol signaling regulates the PKA–CREB axis in fish skeletal muscle, promoting the early transcriptional activation of promyogenic factors. This work underscores the complementary role of rapid cortisol actions in fine-tuning myogenic responses under acute stress, offering new perspectives on muscle plasticity in teleosts.

Source: Fishes

DOI: 10.3390/fishes10120621