TY - JOUR
T1 - A previously uncharacterized role for estrogen receptor β
T2 - Defeminization of male brain and behavior
AU - Kudwa, Andrea E.
AU - Bodo, Cristian
AU - Gustafsson, Jan Åke
AU - Rissman, Emilie F.
PY - 2005/3/22
Y1 - 2005/3/22
N2 - 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.
AB - 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.
KW - Developmental neurobiology
KW - Neuroendocrinology
KW - Sexual differentiation
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U2 - 10.1073/pnas.0500752102
DO - 10.1073/pnas.0500752102
M3 - Article
C2 - 15761056
AN - SCOPUS:15444381068
SN - 0027-8424
VL - 102
SP - 4608
EP - 4612
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -