Division of Developmental & Cognitive Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Horm Behav. 2011 Apr;59(4):528-35. doi: 10.1016/j.yhbeh.2011.02.002. Epub 2011 Feb 18.
Despite the well-documented relation between estradiol (E2) and behavior, exposure to stressors may modify sensitivity to E2. The effects of E2 on behavior are, in part, likely related to their modulation of the serotonin (5HT) and oxytocin systems. The short allele (s-variant) polymorphism found in the promoter region of the SLC6A4 gene that encodes the 5HT transporter (5HTT) modulates responsivity to stressors. The current study used ovariectomized adult female rhesus monkeys to evaluate how exposure to the psychosocial stressor of social subordination and polymorphisms in the gene encoding 5HTT influence the behavioral effects of E2 and immunoreactive serum oxytocin. Dominant females had higher levels of oxytocin than subordinate animals even though E2 increased immunoreactive serum oxytocin in all females. E2 increased affiliative behaviors in all animals, with even more of these prosocial behaviors directed at dominant females. S-variant females, regardless of social status, were more aggressive toward more subordinate cage mates and these behaviors too were increased by E2. Subordinate s-variant females are most often involved in agonistic behavior, less affiliative behavior, and were less responsive to the anxiolytic action of E2. The results show that the short allele of the 5HTT gene synergizes with psychosocial stress exposure to affect the behavioral efficacy of E2 while confirming the actions of E2 for producing generalized behavioral arousal in females. Whether differences in the central action of 5HT and/or oxytocin are responsible for this effect requires further study.
尽管雌二醇（E2）与行为之间存在明确的关系，但暴露于应激源可能会改变对 E2 的敏感性。E2 对行为的影响部分可能与其对 5-羟色胺（5HT）和催产素系统的调节有关。SLC6A4 基因编码 5HT 转运体（5HTT）的启动子区域中发现的短等位基因（s-变体）多态性调节对应激源的反应性。本研究使用去卵巢成年雌性恒河猴来评估社会从属的心理社会应激源暴露以及 5HTT 基因编码多态性如何影响 E2 和免疫反应性血清催产素的行为效应。优势雌性的催产素水平高于从属动物，尽管 E2 增加了所有雌性的免疫反应性血清催产素。E2 增加了所有动物的亲社会行为，而这些亲社会行为中更多的是指向优势雌性。无论社会地位如何，s-变体雌性对更从属的笼伴更具攻击性，而这些行为也会因 E2 而增加。从属的 s-变体雌性最常参与攻击行为，亲社会行为较少，对 E2 的抗焦虑作用反应迟钝。结果表明，5HTT 基因的短等位基因与心理社会应激暴露协同作用，影响 E2 的行为效力，同时证实了 E2 对女性产生广泛行为唤醒的作用。5HT 和/或催产素的中枢作用是否存在差异对此效应负责需要进一步研究。
