Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice
Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice
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DOI：
10.1016/j.yhbeh.2007.11.014
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Silver, Rae
中科院分区：
文献类型：
--
作者：
Iwahana, Eiko;Karatsoreos, Ilia;Silver, Rae
在哺乳动物中，已经确定生理和行为的昼夜节律，包括激素的节律性分泌，由位于下丘脑的视交叉上核（SCN）中的脑时钟调节。虽然SCN调节性腺激素分泌已被充分研究，类固醇激素影响昼夜节律功能的机制还不太清楚。考虑到大量证据表明性激素影响昼夜节律反应的许多方面，并且节律性存在显着的性别差异，这是令人惊讶的。我们先前的发现，SCN的“核心”和“壳”区域在时钟基因的表达上不同，这促使我们研究类固醇受体定位于大脑时钟的特定隔室的可能性，发现雄激素受体（AR）集中在交配小鼠的SCN核心中。在本研究中，我们比较AR表达的雌性和雄性小鼠使用蛋白质印迹和免疫化学。这两种方法都表明AR在男性中的表达比女性高;性腺切除术消除了这些性别差异，雄激素治疗恢复了这些性别差异。在行为水平，性腺切除产生了显着的损失夜间活动开始回合的男性，但没有这样的影响，在女性。用睾酮或非芳香化雄激素二氢睾酮治疗，恢复男性运动活动，消除行为反应的性别差异。结果表明，雄激素调节昼夜节律的反应，并建议SCN网站的行动。(c)2007年爱思唯尔公司All rights reserved.
In mammals, it is well established that circadian rhythms in physiology and behavior, including the rhythmic secretion of hormones, are regulated by a brain clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. While SCN regulation of gonadal hormone secretion has been amply studied, the mechanisms whereby steroid hormones affect circadian functions are less well known. This is surprising considering substantial evidence that sex hormones affect many aspects of circadian responses, and that there are significant sex differences in rhythmicity. Our previous finding that "core" and "shell" regions of the SCN differ in their expression of clock genes prompted us to examine the possibility that steroid receptors are localized to a specific compartment of the brain clock, with the discovery that the androgen receptor (AR) is concentrated in the SCN core in mate mice. In the present study, we compare AR expression in female and male mice using Western blots and immunochemistry. Both of these methods indicate that ARs are more highly expressed in males than in females; gonadectomy eliminates and androgen treatment restores these sex differences. At the behavioral level, gonadectomy produces a dramatic loss of the evening activity onset bout in males, but has no such effect in females. Treatment with testosterone, or with the non-aromatizable androgen dihydrotestosterone, restores male locomotor activity and eliminates sex differences in the behavioral response. The results indicate that androgenic hormones regulate circadian responses, and suggest an SCN site of action. (c) 2007 Elsevier Inc. All rights reserved.