Department of Kinesiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Endocrinology. 2023 Aug 28;164(10). doi: 10.1210/endocr/bqad132.
In males, skeletal muscle function may be altered by shifts in either circulating testosterone or estrogen. We examined the effect of acute (2-week) exposures to 17α-ethinyl estradiol (EE2), an estrogen receptor (ER) agonist, or flutamide, an androgen receptor (AR) antagonist, on the contractile function of individual skeletal muscle fibers from slow-contracting soleus and fast-contracting extensor digitorum longus muscles from adult male mice. Single fiber specific tension (force divided by cross-sectional area) was decreased with flutamide treatment in all myosin heavy chain (MHC) fiber types examined (I, IIA, and IIB); similar effects were observed with EE2 treatment but only in the fastest-contracting MHC IIB fibers. The decreases in maximally Ca2+-activated specific tension were primarily a result of fewer strongly bound myosin-actin cross-bridges, with flutamide treatment also showing lower myofilament lattice stiffness. Myosin-actin cross-bridge kinetics were slower in MHC IIA fibers in flutamide-treated mice, but faster in EE2-treated mice, indicating that contractile velocity may be affected differently in this fiber type, which is commonly expressed in human skeletal muscle. Importantly, these effects were observed in the absence of outcomes previously used to evaluate ER agonists or AR antagonists in rodents including weight of reproductive organs or mammary gland morphology. Our findings indicate that substantial shifts in skeletal muscle function occur in male mice following acute exposures to low doses of a pharmacological ER agonist and an AR antagonist. These results suggest that countermeasures to maintain physical function may be needed early in situations that induce similar ER agonist and AR antagonist conditions.
在男性中，循环睾酮或雌激素的变化可能会改变骨骼肌肉功能。我们研究了急性（2 周）暴露于 17α-乙炔雌二醇（EE2），一种雌激素受体（ER）激动剂，或氟他胺，一种雄激素受体（AR）拮抗剂，对来自成年雄性小鼠的慢收缩比目鱼肌和快收缩趾长伸肌的单个骨骼肌纤维收缩功能的影响。在用氟他胺处理的所有肌球蛋白重链（MHC）纤维类型中（I、IIA 和 IIB），单纤维特定张力（力除以横截面积）降低；在用 EE2 处理时也观察到类似的效果，但仅在最快收缩的 MHC IIB 纤维中观察到。最大 Ca2+激活的特定张力的降低主要是由于结合较弱的肌球蛋白-肌动蛋白横桥减少所致，而氟他胺处理还显示出更低的肌丝晶格刚度。在用氟他胺处理的 MHC IIA 纤维中，肌球蛋白-肌动蛋白交联动力学较慢，但在用 EE2 处理的小鼠中更快，这表明收缩速度可能在这种纤维类型中受到不同的影响，而这种纤维类型在人类骨骼肌中很常见。重要的是，在没有先前用于评估啮齿动物 ER 激动剂或 AR 拮抗剂的结果的情况下观察到这些影响，包括生殖器官或乳腺形态的重量。我们的研究结果表明，在雄性小鼠急性暴露于低剂量药理学 ER 激动剂和 AR 拮抗剂后，骨骼肌功能会发生实质性变化。这些结果表明，在引起类似 ER 激动剂和 AR 拮抗剂条件的情况下，可能需要采取早期措施来维持身体功能。
