首页> 外文期刊>The Journal of Physiology >Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism.
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Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism.

机译:二氢睾丸激素通过依赖ERK1 / 2的机制刺激小鼠骨骼肌纤维中的氨基酸摄取和LAT2的表达。

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摘要

Dihydrotestosterone (DHT) has acuteon-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acuteon-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and alpha-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acuteon-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression.
机译:二氢睾酮(DHT)在成年哺乳动物骨骼肌中具有急性/非基因组作用,其生理功能仍知之甚少。因此,本研究的主要目的是研究DHT对氨基酸摄取的急性/非基因组影响以及在小鼠快,慢肌骨骼肌纤维束中基于这些作用的细胞信号转导事件。使用14C标记氨基酸研究DHT和睾丸激素(T)对氨基酸摄取的影响,并使用药理学干预措施确定介导这些作用的细胞信号转导事件。尽管T对两种纤维类型的异亮氨酸(Ile)和α-甲基氨基异丁酸(MeAIB)的吸收均无影响,但DHT增加了它们在快速拉伸纤维束中的吸收。蛋白质翻译抑制剂,表皮生长因子受体(EGFR),系统A,系统L,mTOR和MEK可逆转这种作用。然而,它对转录抑制剂,雄激素受体和PI3K / Akt相对不敏感。此外,DHT处理增加了两种纤维类型中快速拉伸纤维束中LAT2的表达和EGFR的磷酸化,以及两种纤维类型中ERK1 / 2,RSK1 / 2和ATF2的磷酸化。而且,它降低了两种纤维类型中eEF2的磷酸化并增加了Ile掺入蛋白质的能力。 EGFR和MEK抑制剂可逆转大多数这些作用。从这些发现,我们认为DHT在分离的哺乳动物骨骼肌纤维中的急性/非基因组作用的另一生理功能是刺激氨基酸摄取。这种作用是通过EGFR介导的,涉及MAPK途径的激活和LAT2表达的增加。

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