Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.
Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.
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DOI：
10.1002/jcsm.12843
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Atherton PJ
中科院分区：
文献类型：
--
作者：
Gharahdaghi N;Rudrappa S;Brook MS;Farrash W;Idris I;Aziz MHA;Kadi F;Papaioannou K;Phillips BE;Sian T;Herrod PJ;Wilkinson DJ;Szewczyk NJ;Smith K;Atherton PJ
骨骼肌机械传导与全身激素（如睾酮（T））在调节运动肥大反应中的相对作用存在争议。我们研究了化学内源性T耗竭辅助6周的抗阻运动训练（RET）对年轻男性肌肉质量、功能、生肌调节因子和肌肉合成代谢信号的机械作用。非性腺功能减退男性（n = 16; 18 - 30岁）以双盲方式随机接受安慰剂（P，生理盐水n = 8）或GnRH类似物戈舍瑞林[Zoladex（Z），3.6 mg，n = 8]注射，然后进行6周的监督性全身RET。参与者接受双能X线吸收测定法（DXA），m.股外侧肌（VL）和VL活检，用于评估累积肌肉蛋白合成（MPS）、生肌基因表达和合成代谢信号通路反应。Zoladex将内源性T抑制至性腺功能减退范围内，耐受性良好;抑制与钝化的去脂体重相关[Z：55.4 ± 2.8至55.8 ± 3.1 kg，P = 0.61 vs. P：55.9 ± 1.7至57.4 ± 1.7 kg，P = 0.006，效应量（ES）= 0.31]，复合强度（Z：40 ± 2.3% vs. P：49.8 ± 3.3%，P = 0.03，ES = 1.4），肌肉厚度（Z：2.7 ± 0.4至2.69 ± 0.36 cm，P> 0.99 vs. P：2.74 ± 0.32至2.91 ± 0.32 cm，P <0.0001，ES = 0.48）增加。性腺功能减退减弱了与T代谢相关的肌肉生长分子转导物（例如雄激素受体：Z：1.2倍，P> 0.99 vs. P：1.9倍，P <0.0001，ES = 0.85），抑制/肌生成（例如，IGF-1Ea：Z：1.9倍，P = 0.5 vs. P：3.3倍，P = 0.0005，ES = 0.72; IGF-1Ec：Z：2倍，P> 0.99 vs. P：4.7倍，P = 0.0005，ES = 0.68;肌细胞生成素：Z：1.3倍，P> 0.99 vs. P：2.7倍，P = 0.002，ES = 0.72），RNA/DNA（Z：0.47 ± 0.03至0.53 ± 0.03，P = 0.31对比P：0.50 ± 0.01至0.64 ± 0.04，P = 0.003，ES = 0.72），RNA/ASP（Z：5.8 ± 0.4至6.8 ± 0.5，P> 0.99 vs. P：6.5 ± 0.2至8.9 ± 1.1，P = 0.008，ES = 0.63）比值，以及急性RET诱导的生长信号蛋白磷酸化（例如AKTser473：Z：2.74 ± 0.6，P = 0.2对比P：5.5 ± 1.1倍变化，P <0.001，ES = 0.54和mT0RC1ser2448：Z：1.9 ± 0.8，P> 0.99对比P：3.6 ± 1倍变化，P = 0.002，ES = 0.53）。两个MPS（Z：1.45 ± 0.11至1.50 ± 0.06%·天-1，P = 0.99 vs. P：1.5 ± 0.12至2.0 ± 0.15%·天-1，P = 0.01，ES = 0.97）和（外推）肌肉蛋白分解（Z：93.16 ± 7.8 vs. P：129.1 ± 13.8 g·d-1，P = 0.04，ES = 0.92）减少，性腺功能减退导致净蛋白质周转率较低（3.9 ± 1.1 vs. 1.2 ± 1.1 g·d-1，P = 0.04，ES = 0.95）。我们得出结论，内源性T充足在RET诱导的人类肌肉肥大的分子转导物上调中起着核心作用，这不能通过单独的肌肉机械转导来克服。
The relative role of skeletal muscle mechano‐transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men. Non‐hypogonadal men (n = 16; 18–30 years) were randomized in a double‐blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole‐body RET. Participants underwent dual‐energy X‐ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses. Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF‐1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF‐1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET‐induced phosphorylation of growth signalling proteins (e.g. AKTser473: Z: 2.74 ± 0.6, P = 0.2 vs. P: 5.5 ± 1.1 fold change, P < 0.001, ES = 0.54 and mTORC1ser2448: Z: 1.9 ± 0.8, P > 0.99 vs. P: 3.6 ± 1 fold change, P = 0.002, ES = 0.53). Both MPS (Z: 1.45 ± 0.11 to 1.50 ± 0.06%·day−1, P = 0.99 vs. P: 1.5 ± 0.12 to 2.0 ± 0.15%·day−1, P = 0.01, ES = 0.97) and (extrapolated) muscle protein breakdown (Z: 93.16 ± 7.8 vs. P: 129.1 ± 13.8 g·day−1, P = 0.04, ES = 0.92) were reduced with hypogonadism result in lower net protein turnover (3.9 ± 1.1 vs. 1.2 ± 1.1 g·day−1, P = 0.04, ES = 0.95). We conclude that endogenous T sufficiency has a central role in the up‐regulation of molecular transducers of RET‐induced muscle hypertrophy in humans that cannot be overcome by muscle mechano‐transduction alone.
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DOI：
10.1113/jp272857
发表时间：
2016-12-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Brook MS;Wilkinson DJ;Mitchell WK;Lund JN;Phillips BE;Szewczyk NJ;Greenhaff PL;Smith K;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
4
作者：
Gharahdaghi N;Phillips BE;Szewczyk NJ;Smith K;Wilkinson DJ;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
4.1
作者：
Bass JJ;Wilkinson DJ;Rankin D;Phillips BE;Szewczyk NJ;Smith K;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
4
作者：
Fujiwara, Katsuo;Asai, Hitoshi;Jacobs, Jesse V.
通讯作者：
Jacobs, Jesse V.
DOI：
10.1152/ajpendo.00143.2006
发表时间：
2006-12-01
影响因子：
5.1
作者：
Kvorning, Thue;Andersen, Marianne;Madsen, Klavs
通讯作者：
Madsen, Klavs