ROLES OF ESTROGEN-RECEPTOR ALPHA-GENE EXPRESSION IN REPRODUCTION-RELATED BEHAVIORS IN FEMALE MICE

The role of gene expression of the estrogen receptor-alpha form (ER al pha) in the regulation of female reproductive behavior was investigate d in estrogen receptor knockout (ERKO) mice, deficient specifically fo r the ER alpha, but not the ER beta, gene. Estrogen- or estrogen- plus progesterone-treated gonadectomized ERKO mice did not show any lordos is response. Detailed behavioral analysis revealed that ERKO females w ere also deficient in sexual behavioral interactions preceding the lor dosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resi dent-intruder aggression tests, gonadally intact ERKO females were mor e aggressive toward female intruder mice than wildtype (WT) mice. Gona dectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gona dectomy. However, when mice were tested after gonadectomy for the firs t time, very few ERKO mice showed aggression. In contrast to aggressio n, male-type sexual behavior shown by resident mice toward female intr uder mice during aggression tests was not different between ERKO and W T mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly redu ced levels of parental behavior toward newborn pups placed in their ho me cage. These changes in parental behavior were not influenced by gon adectomy. ERKO females retrieved significantly fewer numbers of pups w ith longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20-65 days a fter gonadectomy. In addition, during parental behavior tests, a signi ficantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER alpha gene expression plays a key role in female mice, not only for sexual behavior but also for other inter related behaviors, such as parental and aggressive behaviors. In addit ion, persistence of genotype differences in parental and aggressive be havior after gonadectomy indicates that ER alpha activation during neu ral developmental processes may also be involved in the regulation of these behaviors.