Nakata Mariko, Ågmo Anders, Sagoshi Shoko, Ogawa Sonoko
Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan.
Research Fellow, Japan Society for Promotion of Science (JSPS), Tokyo, Japan.
Front Behav Neurosci. 2018 Oct 22;12:245. doi: 10.3389/fnbeh.2018.00245. eCollection 2018.
Acquisition of social dominance is important for social species including mice, for preferential access to foods and mates. Male mice establish social rank through agonistic behaviors, which are regulated by gonadal steroid hormone, testosterone, as its original form and aromatized form. It is well known that estrogen receptors (ERs), particularly ER α (ERα), mediate effects of aromatized testosterone, i.e., 17β-estradiol, but precise role played by ER β (ERβ) is still unclear. In the present study, we investigated effects of ERβ gene disruption on social rank establishment in male mice. Adult male ERβ knockout (βERKO) mice and their wild type (WT) littermates were paired based on genotype- and weight-matched manner and tested against each other repeatedly during 7 days experimental period. They underwent 4 trials of social interaction test in neutral cage (homogeneous set test) every other day. Along repeated trials, WT but not βERKO pairs showed a gradual increase of agonistic behaviors including aggression and tail rattling, and a gradual decrease of latency to social rank determination in tube test conducted after each trial of the social interaction test. Analysis of behavioral transition further suggested that WT winners in the tube test showed one-sided aggression during social interaction test suggesting WT pairs went through a process of social rank establishment. On the other hand, a dominant-subordinate relationship in βERKO pairs was not as apparent as that in WT pairs. Moreover, βERKO mice showed lower levels of aggressive behavior than WT mice in social interaction tests. These findings collectively suggest that ERβ may play a significant role in the establishment and maintenance of hierarchical social relationships among male mice.
获得社会优势地位对于包括小鼠在内的社会性物种而言至关重要，因为这有助于优先获取食物和配偶。雄性小鼠通过争斗行为来确立社会等级，而争斗行为受性腺类固醇激素睾酮及其原始形式和芳香化形式的调节。众所周知，雌激素受体（ERs），尤其是ERα，介导芳香化睾酮即17β-雌二醇的作用，但ERβ的确切作用仍不清楚。在本研究中，我们调查了ERβ基因缺失对雄性小鼠社会等级确立的影响。成年雄性ERβ基因敲除（βERKO）小鼠及其野生型（WT）同窝小鼠根据基因型和体重匹配的方式配对，并在7天的实验期内反复相互测试。它们每隔一天在中性笼中进行4次社交互动测试（同组测试）。随着测试的重复进行，WT组（而非βERKO组）的争斗行为（包括攻击和摇尾）逐渐增加，并且在每次社交互动测试后的试管测试中，确定社会等级的潜伏期逐渐缩短。行为转变分析进一步表明，试管测试中的WT获胜者在社交互动测试中表现出单边攻击行为，这表明WT组经历了社会等级确立的过程。另一方面，βERKO组中的优势-从属关系不如WT组明显。此外，在社交互动测试中，βERKO小鼠的攻击行为水平低于WT小鼠。这些发现共同表明，ERβ可能在雄性小鼠等级社会关系的建立和维持中发挥重要作用。
