AROMATASE-ACTIVITY IN DEVELOPING GUINEA-PIG BRAIN - ONTOGENY AND EFFECTS OF EXOGENOUS ANDROGENS

The formation of estrogens from androgens by aromatase in the developi ng brain is an important step in the sexual differentiation of many sp ecies. We characterized aromatase activity (AA) in a high-speed pellet of brain tissue from fetal guinea pig. The apparent substrate affinit y (similar to 17 nM) was comparable to reported values in other specie s. Aromatase activity was highest in the amygdala (AMG) and preoptic a rea (POA), with lesser amounts in the septum (SEPT) and medial basal h ypothalamus (MBH). Activity was low but measurable in parietal cortex (CTX). In the AMG, POA, SEPT, and MBH, AA was highest in early gestati on (Days 35-40) and showed a steady decline through development. No se x difference in AA was apparent. We also determined the effects of adm inistration of exogenous androgens to pregnant females on brain AA in the fetus. Testosterone propionate (5 mg/day on Days 30-39 followed by 1 mg/day on Days 40-50) caused a significant increase (p < 0.05) in A A found in the MBH and CTX. Administration of dihydrotestosterone prop ionate (2.5 mg/day on Days 30-39 followed by 1 mg/day on Days 40-50) s ignificantly stimulated AA in SEPT, MBH, and CTX. These data demonstra te that the fetal guinea pig brain contains high levels of AA during t he critical period of sexual differentiation. Treatment with high leve ls of exogenous androgens consistently induces AA in the MBH and CTX. These latter effects may be among the mechanisms through which exogeno us androgens act on the developing brain.