Cushing Bruce S, Perry Adam, Musatov Sergei, Ogawa Sonoko, Papademetriou Eros
Department of Biology, The University of Akron, Akron, Ohio 44325-3908, USA.
J Neurosci. 2008 Oct 8;28(41):10399-403. doi: 10.1523/JNEUROSCI.1928-08.2008.
Studies using estrogen receptor alpha (ERalpha) knock-out mice indicate that ERalpha masculinizes male behavior. Recent studies of ERalpha and male prosocial behavior have shown an inverse relationship between ERalpha expression in regions of the brain that regulate social behavior, including the medial amygdala (MeA), and the expression of male prosocial behavior. These studies have lead to the hypothesis that low levels of ERalpha are necessary to "permit" the expression of high levels of male prosocial behavior. To test this, viral vectors were used to enhance ERalpha in male prairie voles (Microtus ochrogaster), which display high levels of prosocial behavior and low levels of MeA ERalpha. Adult male prairie voles were transfected with ERalpha in the MeA (MeA-ERalpha) or the caudate-putamen (ERalpha control) or luciferase (MeA-site-specific control), and 3 weeks later tested for spontaneous alloparental behavior and partner preference. Enhancing ERalpha in the MeA altered/reduced male prosocial behavior. Only one-third of MeA-ERalpha males, compared with all control males, were alloparental. MeA-ERalpha males also displayed a significant preference for a novel female. This is a critical finding because the manipulations of neuropeptides, oxytocin and vasopressin, can inhibit the formation of a partner preference, but do not lead to the formation of a preference for a novel female. The results support the hypothesis that low levels of ERalpha are necessary for high levels of male prosocial behavior, and provide the first direct evidence that site-specific ERalpha expression plays a critical role in the expression of male prosocial behavior.
使用雌激素受体α（ERα）基因敲除小鼠的研究表明，ERα使雄性行为男性化。最近关于ERα与雄性亲社会行为的研究显示，在调节社会行为的脑区（包括内侧杏仁核（MeA））中，ERα的表达与雄性亲社会行为的表达呈负相关。这些研究提出了一个假设，即低水平的ERα是“允许”高水平雄性亲社会行为表达所必需的。为了验证这一点，研究人员使用病毒载体增强雄性草原田鼠（Microtus ochrogaster）体内的ERα，这种田鼠表现出高水平的亲社会行为和低水平的MeA ERα。成年雄性草原田鼠在MeA（MeA-ERα）、尾状核-壳核（ERα对照）或荧光素酶（MeA位点特异性对照）中被转染了ERα，3周后测试其自发的异亲行为和伴侣偏好。增强MeA中的ERα改变/降低了雄性亲社会行为。与所有对照雄性相比，只有三分之一的MeA-ERα雄性表现出异亲行为。MeA-ERα雄性对陌生雌性也表现出显著的偏好。这是一个关键发现，因为对神经肽、催产素和加压素的操作可以抑制伴侣偏好的形成，但不会导致对陌生雌性的偏好形成。这些结果支持了低水平的ERα是高水平雄性亲社会行为所必需的这一假设，并提供了首个直接证据，表明位点特异性ERα表达在雄性亲社会行为的表达中起关键作用。
