MODIFICATIONS OF TESTOSTERONE-DEPENDENT BEHAVIORS BY ESTROGEN-RECEPTOR ALPHA-GENE DISRUPTION IN MALE-MICE

The role of the a form of estrogen receptor (ER alpha) gene expression in the regulation of testosterone-dependent male reproductive behavio rs was investigated using ER knockout mice (ERKO), which are specifica lly deficient in functional ER alpha, but not ER beta, gene expression . Previous studies in gonadally intact ERKO mice revealed that male ag gressive behavior was greatly reduced by the lack of a functional ER a lpha gene. In the present study the almost complete suppression of mal e-typical offensive attacks was further confirmed in ERKO mice that ha d been singly housed since weaning. Regarding aggression, it was also found that ER alpha gene disruption virtually abolished the propensity to initiate offensive attacks, even though ERKO mice could elicit att acks from resident C57BL/6J mice as wild-type (WT) and heterozygous li ttermates. Daily injection of testosterone propionate (TP) was complet ely ineffective in inducing aggressive behavior in gonadectomized ERKO mice, whereas it successfully restored aggression in WT mice. In cont rast, male sexual behaviors, mounts and intromissions, were induced by daily injection of TP in both gonadectomized ERKO and WT mice. In add ition to TP, dihydrotestosterone propionate (DHTP) was also effective in restoring mounts in ERKO mice, although DHTP was much more potent i n WT mice than in ERKO mice. Neither TP nor DHTP, however, ever induce d ejaculation in ERKO mice. These results together with previous findi ngs in gonadally intact ERKO mice suggest that ER alpha may be respons ible for the regulation by testosterone of consummatory, but not motiv ational, aspects of male sexual behavior. Finally, ERKO male mice retr ieved newborn pups placed in their home cage with similar latencies to males of the two other genotypes. During parental behavior tests, how ever, a higher percentage of ERKO mice (70%) showed infanticide compar ed with WT mice (35%). The latter result was interpreted as showing th at ER alpha activation by testosterone during the perinatal period may exert a suppressive effect on testosterone-inducible infanticide in a dulthood. With respect to three major testosterone-dependent behaviora l systems reflecting masculinization, these findings demonstrate three different types of effects due to ER alpha gene disruption.