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Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions

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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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  1. Molecular Endocrinology Laboratory, Department of Molecular Cell Biology, K.U. Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, PO Box 901, 3000, Leuven, Belgium

    Vanessa Dubois & Frank Claessens

  2. Division of Gerontology and Geriatrics, Department of Experimental Medicine, K.U. Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Michaël Laurent & Steven Boonen

  3. Division of Experimental Medicine and Endocrinology, K.U. Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Dirk Vanderschueren

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  1. Vanessa Dubois
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Correspondence to Frank Claessens.

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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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