総 説 性ホルモンと骨格筋 相澤 勝治 Sex steroid hormones and skeletal muscle Katsuji Aizawa Received : June 13, 2016 / Accepted : June 27, 2016 Abstract The plasticity of skeletal muscle facilitates adaptation to various stimuli. Sex steroid hormones (androgens and estrogens) are involved in a variety of physiological and pathologi- cal processes. In skeletal muscle, sex steroid hormones affect growth, strength, metabolism, and antioxidant levels and are associated with exercise-induced skeletal muscular adaptation. Sex steroid hormone levels also decrease with aging and are thought to be a factor in muscle atrophy. Though sex steroid hormones play an important role in skeletal muscular homeostasis, the role of the endocrine system in muscle plasticity is unknown. Sex steroid hormones are syn- thesized from cholesterol by steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, with testosterone being irreversibly converted to estrogen by aromatase cytochrome P450 (P450arom). Testosterone is also converted into its bioactive metabolite dihy- drotestosterone (DHT) by 5α-reductase. Sex steroid hormones are produced by various peripher- al target tissues including the kidney, liver, and brain in addition to endocrine organs such as the testis or ovary in the recent research. For instance, steroidogenic enzymes expressed in skeletal muscle have been reported to locally synthesize sex steroid hormones from circulating dehy- droepiandrosterone (DHEA) or testosterone in response to exercise. Thus, local steroidogenesis in skeletal muscle provides further evidence for the presence of an autocrine/paracrine system for sex steroid hormones and their roles in skeletal muscle function and adaptation. This review focuses on the steroidogenesis of skeletal muscle and discusses the physiological significance of the sex steroid hormones network of circulation and skeletal muscle. Jpn J Phys Fitness Sports Med, 65(5): 455-462 (2016) Keywords : steroidogenesis, intracrine organ, exercise 専修大学スポーツ研究所,〒214-8580 神奈川県川崎市多摩区東三田 2-1-1 (Senshu University Institute of Sport, 2-1-1 Higashi-Mita, tama-ku, Kawasaki city, Kanagawa 214-8580, Japan) はじめに 骨格筋は可塑性に富んだ組織であり,運動や不活動な ど様々なストレスに応答変化する.それゆえ,骨格筋の 可塑性メカニズムを明らかにすることは,身体機能の向 上だけでなく,身体活動量の低下や生活習慣病を予防す る上でも重要と考えられる. ヒトの骨格筋は体重の約40%を占める臓器であるが, 近年,運動器としてだけでなく,性ホルモン(アンドロ ゲンとエストロゲン)を産生・分泌する内分泌器官とし ての可能性が示されている 1) .さらに,この骨格筋にお ける性ホルモン産生は運動ストレスによって活性化され ることが報告されている 2, 3) .それゆえ,運動は内分泌腺 だけではなく,骨格筋の性ホルモン合成を刺激し,これ らのネットワークの連携が運動による身体適応に働いて いる可能性が考えられる(Fig. 1).ホルモンは,特定の 臓器(内分泌腺)で作られ,循環血液を介して遠方の標 的組織に作用すると考えられてきたが,局所ホルモン産 生や隣接細胞に作用するパラクリンなどその作用も様々 である.それゆえ,身体運動による骨格筋適応メカニズ ムとして,骨格筋における性ホルモン産生の働きを明ら かにすることは,新たな骨格筋の生物学的役割を示すこ とが出来ると考えられる.本稿では,骨格筋における性 ホルモン産生機序に焦点を当て,運動時応答性やその生 理学的意義について概説する. 性ホルモンの骨格筋作用 性ホルモンは,第二次性徴など心身の性差に作用する. アンドロゲンは,精子形成の促進,男性二次性徴の促進, タンパク質同化作用などが挙げられる.骨格筋における アンドロゲン作用は,除脂肪体重や筋力増加など筋タン パク質合成の亢進 4, 5) ,筋サテライト細胞の増殖 6) ,骨格 体力科学 第65巻 第 5 号 455-462(2016) DOI:10.7600/jspfsm.65.455
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総 説
性ホルモンと骨格筋
相澤 勝治
Sex steroid hormones and skeletal muscleKatsuji Aizawa
Received : June 13, 2016 / Accepted : June 27, 2016
Abstract The plasticity of skeletal muscle facilitates adaptation to various stimuli. Sex steroid hormones (androgens and estrogens) are involved in a variety of physiological and pathologi-cal processes. In skeletal muscle, sex steroid hormones affect growth, strength, metabolism, and antioxidant levels and are associated with exercise-induced skeletal muscular adaptation. Sex steroid hormone levels also decrease with aging and are thought to be a factor in muscle atrophy. Though sex steroid hormones play an important role in skeletal muscular homeostasis, the role of the endocrine system in muscle plasticity is unknown. Sex steroid hormones are syn-thesized from cholesterol by steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, with testosterone being irreversibly converted to estrogen by aromatase cytochrome P450 (P450arom). Testosterone is also converted into its bioactive metabolite dihy-drotestosterone (DHT) by 5α-reductase. Sex steroid hormones are produced by various peripher-al target tissues including the kidney, liver, and brain in addition to endocrine organs such as the testis or ovary in the recent research. For instance, steroidogenic enzymes expressed in skeletal muscle have been reported to locally synthesize sex steroid hormones from circulating dehy-droepiandrosterone (DHEA) or testosterone in response to exercise. Thus, local steroidogenesis in skeletal muscle provides further evidence for the presence of an autocrine/paracrine system for sex steroid hormones and their roles in skeletal muscle function and adaptation. This review focuses on the steroidogenesis of skeletal muscle and discusses the physiological significance of the sex steroid hormones network of circulation and skeletal muscle.
-HSD type I, and P450arom mRNA was revealed by RT-PCR gels in skeletal muscle [gastrocnemius (gastro)] of the rat compared with positive control tissues, namely
-Actin mRNA was used as an internal control.B: Local testosterone when dehydroepiandrosterone are added in cultured muscle cell.C: Local estradiol when dehydroepiandrosterone are added in cultured muscle cell.
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Fig. 2 Skeletal muscle expresses steroidogenic enzymes (ref. [1]).A : mRNA expression of steroidogenic enzymes in various rat tissues. Expression of 3β-HSD, 17β-HSD type I, and P450arom mRNA was revealed by RT-PCR gels in skeletal muscle [gastrocnemius (gastro)] of the rat compared with positive control tissues, namely ovary, testis, liver, kidney, and brain. β-Actin mRNA was used as an internal control.B : Local testosterone when dehydroepiandrosterone are added in cultured muscle cell.C : Local estradiol when dehydroepiandrosterone are added in cultured muscle cell.
459性ホルモンと骨格筋
型糖尿病モデルラットに持久性トレーニングを行った検討では,トレーニング後に骨格筋中のDHEA濃度及びDHT 濃度の増大,空腹時血糖値の減少がみられた.DHTの合成に働く5α-reductaseの阻害剤を投与したトレーニング群では血糖値及びGLUT-4の活性化が抑制されたことから,骨格筋中のDHEA及びDHTは糖代謝の調節に関与している可能性が考えられる35). ヒトを対象とした報告では,Vingren et al.は,若年男女を対象に一過性レジスタンス運動前後における骨格筋内の性ホルモン産生応答について検討し,男女ともに骨格筋中のテストステロン濃度及び17β-HSD,3β-HSDのタンパク質発現は運動前後に明らかな変化を認めなかった36).一方,Sato et al.は,高齢者男性を対象に12週間のレジスタンストレーニングを実施し,加齢に伴い低下した骨格筋内の性ホルモン合成酵素のタンパク質発現の増大,骨格筋中のDHEA濃度,遊離テストステロン濃度,DHT濃度がトレーニングにより増大することを報告した30).とくに運動に対する骨格筋における性ホルモン産生応答は,5α-reductaseを介したDHT産生が身体運動に鋭敏に応答する合成経路の一つとして考えられる3,37).身体運動は骨格筋における性ホルモン産生の活性化因子と考えられるが,対象者,運動タイプ,運動負荷,性差,加齢などの影響を考慮する必要がある.さらに,骨格筋における性ホルモン産生がどのような刺激や調節によって活性化されるかについては今後より詳細な検討が必要と考えられる.
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