Abstract
BackgroundAndrogen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR’s role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified.MethodsFirstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts.Results(1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts.ConclusionsThe study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.
Highlights
Testosterone is widely reported to affect muscle mass, with high level testosterone promoting whereas low level declining muscle mass, mainly via the mediationFu et al Nutr Metab (Lond) (2021) 18:85 of androgen receptor (AR)[1, 2]
The study demonstrated Androgen receptor (AR)’s crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch’s pro-proliferation via activating IGF-1 receptor (IGF-1R)- p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways while decreased AR achieved 20% stretch’s anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass
Under un‐stretched state, AR deficiency slowed down the proliferation rate of myoblasts We firstly confirmed that AR expressed in C2C12 myoblasts whereas no detectable AR was examined in L6 myoblasts (Fig. 1a), consistent with previous studies
Summary
Testosterone is widely reported to affect muscle mass, with high level testosterone promoting whereas low level declining muscle mass, mainly via the mediationFu et al Nutr Metab (Lond) (2021) 18:85 of androgen receptor (AR)[1, 2]. Decrements in serum testosterone or muscle AR during aging are associated with muscle loss[3], and general or muscle-specific AR deletion leads to the decline in muscle mass and strength[4,5,6]. In sedentary states, and in acute or chronic exercise conditions, elevated AR content in skeletal muscle is closely associated with exercise-induced muscle hypertrophy and strength gain [10], and AR blockade or myofiber-specific AR deletion attenuates exerciseinduced increases in muscle mass and strength[11, 12]. Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR’s role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified
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