Abstract
Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca2+ uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions.
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Abbreviations
- AIS:
-
Androgen insensitivity syndrome
- ALP:
-
Alkaline phosphatase
- AMPK:
-
Adenosine monophosphate-activated kinase
- AR:
-
Androgen receptor
- ARE:
-
Androgen response element
- ARKO:
-
Androgen receptor knockout
- BC:
-
Bulbocavernosus
- BSA:
-
Bovine serum albumin
- c-Src:
-
Cellular sarcoma
- EDL:
-
Extensor digitorum logus
- EGFR:
-
Epidermal growth factor receptor
- ERK:
-
Extracellular signal-regulated kinase
- FoxO:
-
Forkhead box O
- Fst:
-
Follistatin
- GH:
-
Growth hormone
- GPCR:
-
G-protein coupled receptor
- IGFBP:
-
IGF binding protein
- IGF-I:
-
Insulin-like growth factor I
- IGF-IR:
-
IGF-I receptor
- IP3:
-
Inositol 1,4,5-triphosphate
- JNK:
-
c-Jun NH2-terminal kinase
- LA:
-
Levator ani
- MADS:
-
Mcm1 agamous deficiens serum response factor
- MAFbx:
-
Muscle Atrophy F-box
- MAPK:
-
Mitogen-activated protein kinase
- mARKO:
-
Myocyte-specific AR knockout
- Mef:
-
Myocyte enhancer factor
- MGF:
-
Mechanogrowth factor
- miR:
-
microRNA
- mRNA:
-
Messenger RNA
- Mst:
-
Myostatin
- mTOR:
-
Mammalian target of rapamycin
- MuRF-1:
-
Muscle Ring Finger 1
- PI3K:
-
Phosphatidylinositol 3-kinase
- PKA:
-
Protein kinase A
- SARM:
-
Selective AR modulator
- SHBG:
-
Sex hormone-binding globulin
- SHBGR:
-
SHBG receptor
- SRC:
-
Steroid receptor coactivator
- SRE:
-
Serum response element
- SRF:
-
Serum response factor
- TCF:
-
T cell factor
- TGF-β:
-
Transforming growth factor-β
- WRE:
-
Wnt response element
- SRE:
-
Serum response element
- SARM:
-
Selective AR modulator
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Acknowledgments
We thank our colleagues of the Molecular Endocrinology Laboratory for many helpful discussions. V. Dubois is holder of a doctoral fellowship of the Fund for Scientific Research Flanders (FWO). S. Boonen and D. Vanderschueren are, respectively, senior clinical investigators of the Fund for Scientific Research Flanders (FWO) and the University hospital of Leuven. S. Boonen is holder of the Leuven University Chair in Gerontology and Geriatrics.
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Dubois, V., Laurent, M., Boonen, S. et al. Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions. Cell. Mol. Life Sci. 69, 1651–1667 (2012). https://doi.org/10.1007/s00018-011-0883-3
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DOI: https://doi.org/10.1007/s00018-011-0883-3