Estradiol derived from testosterone in prenatal life affects the development of catecholamine systems in the frontal cortex in the male rat.

We reported previously that exposure to testosterone (T), neonatally, slows the time-course of development of catecholaminergic activity in the anterior cortex of rat pups. In the present study we assessed the role of T in prenatal life on this development and explored the role of the estrogen metabolite of T, estradiol, in these actions. Male pups born to dams injected daily with 5 mg/kg, s.c., of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), or vehicle only, between gestation days 10 and 21 were either gonadectomized (GX) or anesthetized, only, within 6 h of birth. Dopamine, DOPAC, and noradrenaline levels were assessed, using HPLC-EC, in punched samples taken from cingulate (CING), agranular insular (AID), parietal (PAR) and occipital (OC) cortex on postnatal (PN) days 4 and 10. At PN4 there were no effects of treatment on amine levels, although there were higher levels in frontal areas. At PN10, ATD and ATD GX animals had higher levels of dopamine, DOPAC, and noradrenaline in CING and AID than normal males. It would appear that T acts prenatally through its metabolite, estradiol, to modulate the development of catecholamine activity in the frontal cortex in the neonatal period.