Neonatal septal lesions prevent behavioral defeminization caused by neonatal treatment with estradiol in female rats.

Male rats rarely show lordosis, a female sexual behavior, because of strong inhibition of the behavior in the lateral septum. Because neonatal treatment with estradiol (E2) in female rats decreases lordosis, it is believed that the lateral septum is a target of E2 action to defeminize or masculinize the lordosis-inhibiting system. Here, we tested the hypothesis that disruption of the lateral septum before E2 treatment prevents the effect of neonatal E2 on lordosis. Female rats that underwent radiofrequency-induced septal lesions or sham operation on postnatal day 4 (PD4, day of birth = PD1) were subcutaneously injected with E2 or sesame oil vehicle alone on PD5. Vaginal opening and smears were checked. After sexual maturation, lordosis tests were performed. The effects of neonatal septal lesions on lordosis in male rats were also observed. Sham-operated and E2-treated female rats showed a reduction in lordosis and irregular estrous cycles. Conversely, septal lesioned and E2-treated females exhibited higher levels of lordosis, although their estrous cycles were irregular. These results suggest that neonatal septal lesions prevent females from being behaviorally defeminized by neonatal E2. Additionally, neonatally septal lesioned males displayed higher levels of lordosis than sham-operated males. These results suggest that E2, which is produced by the aromatization of testicular testosterone in the neonatal period, acts on the lateral septum to organize the lordosis-inhibiting system.