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Local biosynthesis of corticosterone in rat skeletal muscle.
The Journal of Steroid Biochemistry and Molecular Biology ( IF 2.7 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.jsbmb.2020.105693
Michiko Sato 1 , Kimikazu Sugiyama 2 , Naoyuki Maeda 3 , Jumpei Fujiki 2 , Takahiro Ieko 2 , Yoshio Kawamura 4 , Hidetomo Iwano 2 , Kuniaki Mukai 5 , Hiroshi Yokota 2
Affiliation  

Adrenal corticosterone plays crucial roles in energy metabolism and immuno-reactivity throughout the body. As we have previously shown that corticosterone biosynthesis in C2C12 myoblasts, we study about corticosterone biosynthesis in rat skeletal muscles. It was found that enzymatic activities producing corticosterone and testosterone except the activity of P450scc in rat skeletal muscle as like as C2C12 cells. The CYP11B mRNA encoding cytochrome P45011β that mediates 11-deoxycorticosterone hydroxylase activity, producing corticosterone was expressed in skeletal muscles. In immunoblotting analysis, cytochrome P45011β protein was expressed in rat muscles and whole organs especially higher levels in adrenal and brain. The localizations of corticosterone content and enzymatic activities involved in the production of corticosterone were preferentially observed in gastrocnemius fibers rather than in soleus fibers. The immunohistochemical analysis showed that the fast-twitch or type II muscle fibers positive to antibody against fast myosin heavy chain were preferentially stained with anti-cytochrome P45011β antibody in the gastrocnemius fiber. In addition, we detected corticosterone biosynthesis from pregnenolone sulfate conjugates in perfusion of the rat hindquarter. Corticosterone is synthesized in rat skeletal muscles and the biosynthesis was localized in the fast-twitch or type II muscle fibers. We speculated that the local synthesized corticosterone might be involved in glucocorticoid-induced muscle atrophy that preferentially occurs in fast muscle fibers, and the initial substrate of the local CORT biosynthesis were supported to be performed from the conjugates such as pregnenolone sulfate circulating in the blood flow.

中文翻译:

皮质酮在大鼠骨骼肌中的局部生物合成。

肾上腺皮质激素在全身能量代谢和免疫反应中起关键作用。如我们先前所显示的,C2C12成肌细胞中皮质酮的生物合成,我们研究了大鼠骨骼肌中皮质酮的生物合成。已经发现,除了P450scc在大鼠骨骼肌中的活性外,酶活性还产生皮质酮和睾丸激素,如C2C12细胞。CYP11B mRNA编码介导11-脱氧皮质酮羟化酶活性,产生皮质酮的细胞色素P45011β,在骨骼肌中表达。在免疫印迹分析中,细胞色素P45011β蛋白在大鼠的肌肉和整个器官中表达,尤其在肾上腺和大脑中表达较高。优先在腓肠肌纤维中而不是在比目鱼肌中观察到涉及皮质酮生产的皮质酮含量和酶活性的局部化。免疫组织化学分析显示,对腓肠肌纤维中抗快速肌球蛋白重链抗体呈阳性的快肌或II型肌纤维优先被抗细胞色素P45011β抗体染色。此外,我们在大鼠后肢的灌注中检测到了由孕烯醇酮硫酸盐共轭物合成的皮质酮。皮质酮是在大鼠骨骼肌中合成的,其生物合成位于快肌或II型肌纤维中。我们推测,本地合成的皮质酮可能与糖皮质激素诱发的肌肉萎缩有关,后者优先发生在快速肌肉纤维中,
更新日期:2020-05-11
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