Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats
Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats
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DOI：
10.1152/ajpendo.00367.2006
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发表时间：
2007-02-01
影响因子：
5.1
通讯作者：
Mesaki, Noboru
中科院分区：
文献类型：
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作者：
Aizawa, Katsuji;Iemitsu, Motoyuki;Mesaki, Noboru
来自性腺外组织的性类固醇激素（睾酮和雌激素）的功能重要性最近得到了显着的重视。循环脱氢表雄酮（DHEA）被外周吸收并通过3 β-羟基类固醇脱氢酶（HSD）和17 β-HSD转化为睾酮，睾酮又通过芳香酶细胞色素P-450（P450 arom）不可逆地转化为雌激素。虽然性类固醇激素与骨骼肌的调节和适应有关，但目前尚不清楚骨骼肌是否具有能够代谢循环DHEA的局部类固醇生成酶机制。因此，在这里，我们调查是否三个关键的类固醇生成酶（3 β-HSD，17 β-HSD，和P450 arom）存在于骨骼肌，并能够产生性类固醇激素。与我们的假设相一致，本研究表明，这些酶的mRNA和蛋白质表达在大鼠骨骼肌细胞在体内和培养（体外）。重要的是，我们还显示了在培养的肌肉细胞中以剂量依赖性方式从脱氢表雄酮或睾酮在细胞内形成睾酮和雌二醇。这些发现是新颖的和重要的，因为它们提供了第一个证据表明骨骼肌能够从循环DHEA或睾酮局部合成性类固醇激素。
The functional importance of sex steroid hormones ( testosterone and estrogens), derived from extragonadal tissues, has recently gained significant appreciation. Circulating dehydroepiandrosterone ( DHEA) is peripherally taken up and converted to testosterone by 3 beta-hydroxysteroid dehydrogenase (HSD) and 17 beta-HSD, and testosterone in turn is irreversibly converted to estrogens by aromatase cytochrome P-450 (P450arom). Although sex steroid hormones have been implicated in skeletal muscle regulation and adaptation, it is unclear whether skeletal muscles have a local steroidogenic enzymatic machinery capable of metabolizing circulating DHEA. Thus, here, we investigate whether the three key steroidogenic enzymes (3 beta-HSD, 17 beta-HSD, and P450arom) are present in the skeletal muscle and are capable of generating sex steroid hormones. Consistent with our hypothesis, the present study demonstrates mRNA and protein expression of these enzymes in the skeletal muscle cells of rats both in vivo and in culture ( in vitro). Importantly, we also show an intracellular formation of testosterone and estradiol from DHEA or testosterone in cultured muscle cells in a dose-dependent manner. These findings are novel and important in that they provide the first evidence showing that skeletal muscles are capable of locally synthesizing sex steroid hormones from circulating DHEA or testosterone.