Testosterone boosts physical activity in male mice via dopaminergic pathways.
Testosterone boosts physical activity in male mice via dopaminergic pathways.
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睾丸激素通过多巴胺能途径增强雄性小鼠的体育活动。
DOI：
10.1038/s41598-017-19104-0
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Vanderschueren D
中科院分区：
文献类型：
--
作者：
Jardí F;Laurent MR;Kim N;Khalil R;De Bundel D;Van Eeckhaut A;Van Helleputte L;Deboel L;Dubois V;Schollaert D;Decallonne B;Carmeliet G;Van den Bosch L;D'Hooge R;Claessens F;Vanderschueren D
男性体内睾酮(T)水平低，尤其是其游离部分，与能量损失有关。与此相一致的是，啮齿动物的兰花切除会导致体力活动减少。尽管如此，T刺激活动的机制仍然大多不清楚。在这里，我们研究了三种不同的雄激素缺乏小鼠模型：ORX，雄激素受体(AR)基因敲除(ARKO)和性激素结合球蛋白(SHBG)转基因小鼠，一种新的“低游离T”小鼠模型的自愿跑轮行为。我们的结果清楚地显示了T刺激轮运行的快速和戏剧性的作用，这不能用它对肌肉的作用来解释，神经肌肉研究和肌肉特异性条件性ARKO小鼠模型证明了这一点。T的作用通过其游离部分发生，如在SHBG转基因小鼠中的结果所示，它暗示了雄激素和雌激素途径。基因表达和功能研究都表明，T调节体内对多巴胺(DA)激动剂的敏感性。此外，多巴胺拮抗剂可抑制T轮的运动恢复。这些发现表明，T的游离部分通过AR或间接通过芳构化为雌激素，通过作用于中枢DA通路刺激雄性小鼠的身体活动行为。
Low testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of “low free T”. Our results clearly show a fast and dramatic action of T stimulating wheel running, which is not explained by its action on muscle, as evidenced by neuromuscular studies and in a muscle-specific conditional ARKO mouse model. The action of T occurs via its free fraction, as shown by the results in SHBG-transgenic mice, and it implies both androgenic and estrogenic pathways. Both gene expression and functional studies indicate that T modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the restoration of wheel running by T is inhibited by treatment with DA antagonists. These findings reveal that the free fraction of T, both via AR and indirectly through aromatization into estrogens, stimulates physical activity behavior in male mice by acting on central DA pathways.
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影响因子：
3
作者：
James MH;Campbell EJ;Walker FR;Smith DW;Richardson HN;Hodgson DM;Dayas CV
通讯作者：
Dayas CV
DOI：
10.1056/nejmoa1000485
发表时间：
2010-07-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Basaria S;Coviello AD;Travison TG;Storer TW;Farwell WR;Jette AM;Eder R;Tennstedt S;Ulloor J;Zhang A;Choong K;Lakshman KM;Mazer NA;Miciek R;Krasnoff J;Elmi A;Knapp PE;Brooks B;Appleman E;Aggarwal S;Bhasin G;Hede-Brierley L;Bhatia A;Collins L;LeBrasseur N;Fiore LD;Bhasin S
通讯作者：
Bhasin S
影响因子：
3.5
作者：
Iwahana, Eiko;Karatsoreos, Ilia;Silver, Rae
通讯作者：
Silver, Rae
影响因子：
4.8
作者：
Konkle, Anne T. M.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
影响因子：
29
作者：
Fernandes, Maria Fernanda A.;Matthys, Dominique;Fulton, Stephanie
通讯作者：
Fulton, Stephanie