To study the function of activin E, a TGF-beta superfamily member, in the regulation of affective behavior, we investigated the behavior of transgenic mice overexpressing activin E (TgAct beta E mice). Male TgAct beta E mice showed aggressive behavior in resident-intruder tests. In elevated plus-maze tests, the percentage of open arm entries was significantly increased in female TgAct beta E mice compared with that in wild-type mice. Furthermore, female TgAct beta E mice stayed in the central area for a significantly longer time than wild-type mice in open held tests. These results indicated that TgAct beta E mice had less anxiety-like behavior. The number of restraint-stress-evoked c-Fos-positive cells in the hypothalamic paraventricular nucleus in TgAct beta E mice was significantly decreased compared with that in wild-type mice. This suggests that synthesis of corticotrophin-releasing hormone induced by stress was decreased in TgAct beta E mice. Taking these results together, activin E may act as a regulator of the hypothalamic-pituitary-adrenal axis. (C) 2009 Elsevier Inc. All rights reserved.