Title: Role of Estrogen Receptors in Aggressive Behaviors
Name: Sonoko Ogawa
The Rockefeller University
1230 York Avenue
New York, NY 10021
Year: 1996, 1997
Type: Research Grant

Our research focus has been in the understanding of differential regulation of aggressive behavior by two types of estrogen receptors, ER-α and ER-β. ERs, as a member of the nuclear receptor superfamily, are involved in transcriptional regulation of various gene products. It has been known for some time that testosterone is a major factor to facilitate aggressive behavior in most species, including humans. Since testosterone not only acts on brain androgen receptors in its original form but can also be aromatized to estradiol in the brain, it has been hypothesized that estrogen receptor (classical ER-α) mediated action of gonadal steroid hormones may also be involved in the regulation of aggressive behavior. The recent discovery of a second form of estrogen receptor, ER-β, however, further complicated the role played by nuclear steroid receptors in the regulation of aggressive behavior. Using mice that lack either ER-α or ER-β genes, we found that two types of ER may have an opposite effect on aggressive behavior. Specifically, mice lacking ER-α genes were not aggressive at all, whereas those lacking ER-β genes were more aggressive than control littermate mice, particularly during puberty and young adult ages. These findings suggest that activation of ER-α is necessary for the induction of aggressive behavior, whereas activation of ER-β may inhibit aggressive behavior in male mice. It is assumed that ER-α activation at the perinatal critical period for sexual differentiation of brain development is essential for expression of male-typical aggressive behavior. On the other hand, ER-β's role is more of a modulatory one to fine-tune the final outcome of the behavior by affecting animals' anxiety levels as well as social memory/learning ability. Our recent studies suggest that ER-β may inhibit aggression by modifying the synthesis and secretion of neuropeptides, oxytocin, and vasopressin, as well as a neurotransmitter, serotonin.

Bibliography: Ogawa et al., PNAS, 94, 1476-1481, 1997.
Ogawa et al., PNAS, 96, 12887-12892, 1999.
Ogawa et al., PNAS, 97, 14737-14741, 2000.
Ogawa et al., Current Opinions of Endocrinology and Diabetes, 9, 224-229.
Nomura et al., Hormones and Behavior, 41, 288-296, 2002.