Anabolic effects of testosterone are preserved during inhibition of 5α-reductase
Anabolic effects of testosterone are preserved during inhibition of 5α-reductase
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DOI：
10.1152/ajpendo.00130.2007
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发表时间：
2007-08-01
影响因子：
5.1
通讯作者：
Wronski, Thomas J.
中科院分区：
文献类型：
--
作者：
Borst, Stephen E.;Conover, Christine F.;Wronski, Thomas J.
在替代剂量下，睾酮只能适度增加老年性腺功能减退男性的肌肉力量和骨密度。虽然较高剂量的睾酮合成代谢作用更强，但人们担心会增加不良反应，特别是前列腺肥大。我们测试了一种新的策略，以获得强大的合成代谢作用，而不前列腺肿大。睾丸切除（ORX）雄性大鼠接受1.0 mg睾酮/天给药56天，同时给予和不给予0.75 mg 5 α-还原酶抑制剂MK-434。给药替尼可升高前列腺双氢睾酮浓度并导致前列腺增大。MK-434可抑制这两种作用。ORX产生分解代谢状态，表现为摄食量减少、体重增加减缓、血红蛋白浓度降低、肾脏质量降低和骨吸收增加，胫骨近端松质骨体积减少和小梁数量减少。在比目鱼肌和趾长伸肌中，ORX降低了I型肌纤维的百分比和1型和2型纤维的横截面积。替西莫司给药引起了许多合成代谢效应，包括食物摄入量、血红蛋白浓度和握力的增加，并逆转了ORX对骨的分解代谢效应。替吉奥给药也部分逆转了ORX诱导的肌纤维变化。与睾酮的前列腺效应相反，MK-434未阻断睾酮对肌肉、骨和血红蛋白浓度的影响。我们的研究表明，睾酮对肌肉和骨骼的影响可以从前列腺的影响中分离出来，并提供了一个可测试的策略，用于对抗老年性腺功能减退男性的肌肉减少和骨质减少。
At replacement doses, testosterone produces only modest increases in muscle strength and bone mineral density in older hypogonadal men. Although higher doses of testosterone are more anabolic, there is concern over increased adverse effects, notably prostate enlargement. We tested a novel strategy for obtaining robust anabolic effects without prostate enlargement. Orchiectomized (ORX) male rats were treated for 56 days with 1.0 mg testosterone/day, with and without 0.75 mg/day of the 5 alpha-reductase inhibitor MK-434. Testosterone administration elevated the prostate dihydrotestosterone concentration and caused prostate enlargement. Both effects were inhibited by MK-434. ORX produced a catabolic state manifested in reduced food intake, blunted weight gain, reduced hemoglobin concentration, decreased kidney mass, and increased bone resorption, and in the proximal tibia there was both decreased cancellous bone volume and a decreased number of trabeculae. In soleus and extensor digitorum longus muscles, ORX reduced both the percentage of type I muscle fibers and the cross-sectional area of type 1 and 2 fibers. Testosterone administration caused a number of anabolic effects, including increases in food intake, hemoglobin concentration, and grip strength, and reversed the catabolic effects of ORX on bone. Testosterone administration also partially reversed ORX-induced changes in muscle fibers. In contrast to the prostate effects of testosterone, the effects on muscle, bone, and hemoglobin concentration were not blocked by MK-434. Our study demonstrates that the effects of testosterone on muscle and bone can be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.