title: A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior.
abstract: 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 beta (ERbeta). Adult male ERbeta knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ERbeta 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 ERbeta is involved in defeminization of brain and behavior. This aspect of ERbeta function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.
authors.affiliation: Program in Neuroscience, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Kudwa
authors.forename: Cristian
authors.initials: C
authors.lastname: Bodo
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Emilie F
authors.initials: EF
authors.lastname: Rissman
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009919:Orchiectomy; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000502:physiology*; D012903:Smell / Q000502:physiology; D013737:Testis / Q000502:physiology
chemical_list: D047629:Estrogen Receptor beta