The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

Abstract

Glucocorticoids (GCs) strongly regulate myostatin transcript levels in mammals via glucocorticoid response elements (GREs) in the myostatin promoter, and bioinformatics methods suggest that this regulatory mechanism is conserved among many vertebrates. However, the multiple myostatin genes found in some fishes may be an exception. In rainbow trout (Oncorhynchus mykiss), two genome duplication events have produced three putatively functional myostatin genes, myostatin-1a, -1b and -2a, which are ubiquitously and differentially expressed. In addition, in silico promoter analyses of the rainbow trout myostatin promoters have failed to identify putative GREs, suggesting a divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA expression is not regulated by glucocorticoids in rainbow trout. In this study, both juvenile rainbow trout and primary trout myoblasts were treated with cortisol to examine the relationship between this glucocorticoid and myostatin mRNA expression. Results suggest that exogenous cortisol does not regulate myostatin-1a and -1b expression in vivo, as myostatin mRNA levels were not significantly affected by cortisol treatment in either red or white muscle tissue. In red muscle, myostatin-2a levels were significantly elevated in the cortisol treatment group relative to the control, but not the vehicle control, at both 12 h and 24 h post-injection. As such, it is unclear if cortisol was acting alone or in combination with the vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in vitro. Further work is needed to determine if this response is the direct result of cortisol acting on the myostatin-1b promoter or through an alternative mechanism. These results suggest that regulation of myostatin by cortisol may not be as highly conserved as previously thought and support previous work that describes potential functional divergence of the multiple myostatin genes in fishes.

Glucocorticoid and mineralocorticoid receptor activation modulates postnatal growth

“…These results support the conserved role of GR activation as a key mediator of muscle wasting and negative protein balance in response to excess GCs during chronic stress (Kuo et al 2013). Neither cortisol treatment nor genotype had an effect on mystnb; however, the role of mystnb in teleost is thought to be divergent from its role in mammals (Galt et al 2014).…”

mRNA-seq reveals skeletal muscle atrophy in response to handling stress in a marine teleost, the red cusk-eel (Genypterus chilensis)

“…In mammals, in vitro models have been very useful in defining the glucocorticoid pathway by reducing complexity, as compared to an in vivo model [ 43 , 44 ]. Similarly, fish myotubes primary culture has been used as a valid model for understanding the signaling pathways involved in muscle development and growth in teleost, including for glucose transport [ 45 ], TOR signaling [ 46 ], IGF-1 signaling [ 47 – 49 ], Myostatin signaling [ 50 , 51 ], GH signaling [ 52 ], proinflammatory cytokine signaling [ 53 ], PAMPs signaling [ 54 ], and cortisol signaling [ 55 ]. Similarly, in the present study using an in vitro model, it was determined that cortisol through the expression of components of the ubiquitin-proteasome and autophagy-lysosome systems was an inductor of skeletal muscle atrophy in fish,.…”

Loss of the glucocorticoid receptor in zebrafish improves muscle glucose availability and increases growth

“…While there are orthologs of these genes in fish, it is unknown whether these genes are under transcriptional control of GR. Indeed, there is evidence to suggest that the function of these genes, in particular, myostatin (mystnb), is not conserved in lower vertebrates (20). A direct role of GR signaling in modulating weight changes comes from conditional knockouts and pharmacological studies in mammals.…”