A previously uncharacterized role for estrogen receptor β: Defeminization of male brain and behavior

Andrea E. Kudwa, Cristian Bodo, Jan Åke Gustafsson, Emilie F. Rissman

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Sex differences in brain and behavior are ubiquitous in sexually reproducing species. One cause of sexual dimorphisms is developmental differences in circulating concentrations of gonadal steroids. Neonatal testes produce androgens; thus, males are exposed to both testosterone and estradiol, whereas females are not exposed to high concentrations of either hormone until puberty. Classically, the development of neural sex differences is initiated by estradiol, which activates two processes in male neonates; masculinization, the development of male-type behaviors, and defeminization, the loss of the ability to display female-type behaviors. Here, we test the hypothesis that defeminization is regulated by estrogen receptor β(ERβ). Adult male ERβ knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ERβ knockout mice showed significantly higher levels of female receptivity as compared with WT littermates. Testes-intact males did not differ in any aspects of their male sexual behavior, regardless of genotype. In olfactory preference tests, males of both genotypes showed equivalent preferences for female-soiled bedding. Based on these results, we hypothesize that ERβ is involved in defeminization of brain and behavior. This aspect of ERβ function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.

Original languageEnglish (US)
Pages (from-to)4608-4612
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 22 2005


  • Developmental neurobiology
  • Neuroendocrinology
  • Sexual differentiation

ASJC Scopus subject areas

  • Genetics
  • General


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