Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny

Abstract

Testosterone (T) and estradiol (E 2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behavior via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E 2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E 2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of male fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant difference between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups. At day 1 SAL males show higher AA in the Am than in the hypothalamus (POA + AH), whereas in the LAL strain the AA did not differ between these brain areas. In the LAL males plasma T levels decreased from E17 to day 1, whereas the SAL neonates (day 1) exhibited higher circulating T concentrations than LAL neonates. These results suggest a T-independent aromatase induction prenatally in both selection lines, whereas neonatally the higher plasma T level in the SAL line coincides with higher AA levels in the Am. Accordingly, a differential pattern of E 2 formation exists in the brains of the two selection lines during ontogeny. The variation in circulating T and maximal brain E 2 formation around birth might result in a differential organization of adult CNS sensitivity to sex steroids and accordingly differences in aggressive behavior.