For those looking for a deeper understanding, here's an eyeful....
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376019/
Notably, glucocorticoids induce atrophy by upregulating REDD-1 and, importantly Kruppel-Like Factor 15, which lead to a marked decrease in mTOR and an increase in amino acid mobilization for gluconeogensis. This causes muscle atrophy. Another side effect of excessive glucocorticoid activation is an upregulation of FOXO (and it's downstream target 4E-BP1, which prevents "excessive" fat burning, potential leading to the incredible fat gain noted).
Pulse dosing prevents blunting of IGF-1 induced mTOR activation and enhancement of anabolic pathways.
Am J Pathol. 2017 Aug 18. pii: S0002-9440(17)30529-1. doi: 10.1016/j.ajpath.2017.07.017. [Epub ahead of print]
Intermittent Glucocorticoid Dosing Improves Muscle Repair and Function in Mice with Limb-Girdle Muscular Dystrophy.
Quattrocelli M1, Salamone IM1, Page P1, Warner JL1, Demonbreun AR1, McNally EM2.
Author information
Abstract
The muscular dystrophies are genetically diverse. Shared pathological features among muscular dystrophies include breakdown, or loss of muscle, and accompanying fibrotic replacement. Novel strategies are needed to enhance muscle repair and function and to slow this pathological remodeling. Glucocorticoid steroids, like prednisone, are known to delay loss of ambulation in patients with Duchenne muscular dystrophy but are accompanied by prominent adverse effects. However, less is known about the effects of steroid administration in other types of muscular dystrophies, including limb-girdle muscular dystrophies (LGMDs). LGMD 2B is caused by loss of dysferlin, a membrane repair protein, and LGMD 2C is caused by loss of the dystrophin-associated protein, γ-sarcoglycan. Herein, we assessed the efficacy of steroid dosing on sarcolemmal repair, muscle function, histopathology, and the regenerative capacity of primary muscle cells. We found that in murine models of LGMD 2B and 2C, daily prednisone dosing reduced muscle damage and fibroinflammatory infiltration. However, daily prednisone dosing also correlated with increased muscle adipogenesis and atrophic remodeling. Conversely, intermittent dosing of prednisone, provided once weekly, enhanced muscle repair and did not induce atrophy or adipogenesis, and was associated with improved muscle function. These data indicate that dosing frequency of glucocorticoid steroids affects muscle remodeling in non-Duchenne muscular dystrophies, suggesting a positive outcome associated with intermittent steroid dosing in LGMD 2B and 2C muscle.
Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
J Clin Invest. 2017 Jun 1;127(6):2418-2432. doi: 10.1172/JCI91445. Epub 2017 May 8.
Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy.
Quattrocelli M, Barefield DY, Warner JL, Vo AH, Hadhazy M, Earley JU, Demonbreun AR, McNally EM.
Abstract
Glucocorticoid steroids such as prednisone are prescribed for chronic muscle conditions such as Duchenne muscular dystrophy, where their use is associated with prolonged ambulation. The positive effects of chronic steroid treatment in muscular dystrophy are paradoxical because these steroids are also known to trigger muscle atrophy. Chronic steroid use usually involves once-daily dosing, although weekly dosing in children has been suggested for its reduced side effects on behavior. In this work, we tested steroid dosing in mice and found that a single pulse of glucocorticoid steroids improved sarcolemmal repair through increased expression of annexins A1 and A6, which mediate myofiber repair. This increased expression was dependent on glucocorticoid response elements upstream of annexins and was reinforced by the expression of forkhead box O1 (FOXO1). We compared weekly versus daily steroid treatment in mouse models of acute muscle injury and in muscular dystrophy and determined that both regimens provided comparable benefits in terms of annexin gene expression and muscle repair. However, daily dosing activated atrophic pathways, including F-box protein 32 (Fbxo32), which encodes atrogin-1. Conversely, weekly steroid treatment in mdx mice improved muscle function and histopathology and concomitantly induced the ergogenic transcription factor Krüppel-like factor 15 (Klf15) while decreasing Fbxo32. These findings suggest that intermittent, rather than daily, glucocorticoid steroid regimen promotes sarcolemmal repair and muscle recovery from injury while limiting atrophic remodeling.
PMID:
28481224
PMCID:
PMC5451235
DOI:
10.1172/JCI91445
Free PMC Article
Now, the studies suggest weekly dosing, but these are in children and muscular dystrophy patients. With the higher demands that we athletes place on these pathways, we are starting with twice a week dosing to initiate anabolic signals and prevent daily dose induced atrophic and adipogenic signals.