Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice.
Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice.
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DOI：
10.1016/j.yhbeh.2008.07.013
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发表时间：
2008-11
影响因子：
3.5
通讯作者：
Walf AA
中科院分区：
文献类型：
--
作者：
Frye CA;Koonce CJ;Edinger KL;Osborne DM;Walf AA
替吉奥（T）及其代谢产物可能对焦虑和认知有一些有益的作用，但这些作用的机制尚不清楚。T被还原为二氢睾酮（DHT），后者可转化为5α-雄甾烷，3α，17 β-二醇（3α-二醇）和/或5α-雄甾烷-3 β，17 β-二醇（3β-二醇）。此外，T可以转化为雄烯二酮，然后转化为雄酮。这些代谢产物以不同的亲和力与雄激素受体（AR; T和DHT）、雌激素受体（ERβ; 3α-二醇、3β-二醇）或GABAA/苯二氮卓类受体（GBR; 3α-二醇、雄酮）结合。进行了三个实验以研究减少焦虑样和增强认知表现可能部分归因于T代谢物对ERβ的作用的假设。实验一：性腺切除（GDX）野生型和ERβ敲除小鼠（βERKO）每周皮下（SC）给予3α-二醇、3β-二醇、雄酮或油溶剂，并在焦虑任务（旷场、高架十字迷宫、明暗转换）或物体识别任务中测试认知表现。实验二：GDX大鼠皮下注射3α-二醇、3β-二醇、雄酮或油溶剂，并进行相同的任务测试。实验三：GDX大鼠雄酮或媒介物引发和管理的AR（氟替卡松），ER（他莫昔芬），或GBR（氟马西尼），或媒介物的拮抗剂，然后在高架十字迷宫测试。大鼠和野生型小鼠，但不是βERKO小鼠，在物体识别任务中始终具有减少的焦虑和提高的表现。雄甾酮仅有效减少高架十字迷宫中的焦虑样行为，氟马西尼给药可适度降低该作用。因此，ERβ的作用可能是T减少焦虑和增强认知的作用所必需的。
Testosterone (T) and its metabolites may underlie some beneficial effects for anxiety and cognition, but the mechanisms for these effects are unclear. T is reduced to dihydrotestosterone (DHT), which can be converted to 5α-androstane,3α,17β-diol (3α-diol) and/or 5α-androstane-3β,17β-diol (3β-diol). Additionally, T can be converted to androstenedione, and then to androsterone. These metabolites bind with varying affinity to androgen receptors (ARs; T and DHT), estrogen receptors (ERβ; 3α-diol, 3β-diol), or GABAA/benzodiazepine receptors (GBRs; 3α-diol, androsterone). Three experiments were performed to investigate the hypothesis that reduced anxiety-like and enhanced cognitive performance may be due in part to actions of T metabolites at ERβ. Experiment 1: Gonadectomized (GDX) wildtype and ERβ knockout mice (βERKO) were subcutaneously (SC) administered 3α-diol, 3β-diol, androsterone, or oil vehicle at weekly intervals, and tested in anxiety tasks (open field, elevated plus maze, light–dark transition) or for cognitive performance in the object recognition task. Experiment 2: GDX rats were administered SC 3α-diol, 3β-diol, androsterone, or oil vehicle, and tested in the same tasks. Experiment 3: GDX rats were androsterone- or vehicle-primed and administered an antagonist of ARs (flutamide), ERs (tamoxifen), or GBRs (flumazenil), or vehicle and then tested in the elevated plus maze. Both rats and wildtype mice, but not βERKO mice, consistently had reduced anxiety and improved performance in the object recognition task. Androsterone was only effective at reducing anxiety-like behavior in the elevated plus maze and this effect was modestly reduced by flumazenil administration. Thus, actions at ERβ may be required for T’s anxiety-reducing and cognitive-enhancing effects.
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影响因子：
1.9
作者：
Frye, CA;Walf, AA
通讯作者：
Walf, AA
影响因子：
3.6
作者：
Edinger, KL;Lee, B;Frye, CA
通讯作者：
Frye, CA
影响因子：
2.7
作者：
Ceccarelli, I;Scaramuzzino, A;Aloisi, AM
通讯作者：
Aloisi, AM
影响因子：
3.7
作者：
Delhez, M;Hansenne, M;Legros, JJ
通讯作者：
Legros, JJ
影响因子：
3.6
作者：
Frye, CA;Edinger, KL
通讯作者：
Edinger, KL