REGULATION OF AROMATASE GENE-EXPRESSION IN THE ADULT-RAT BRAIN

Brain aromatase plays an important role in the regulation of adult rep roductive behavior in male rodents, This report focuses on recent expe riments from our laboratory that examined the distribution and regulat ion of aromatase mRNA in the rat brain. Aromatase mRNA was measured by a highly sensitive ribonuclease protection assay using a P-32-labeled antisense RNA probe that was complimentary to the 5' coding region of rat aromatase mRNA. This probe protects two RNA fragments in rat brai n tissue: a 430-nt length fragment and a shorter 300-nt fragment. The presence of the 300-nt RNA fragment is not associated with enzyme acti vity in the rat brain and appears to represent an alternative brain-sp ecific aromatase transcript whose function, if any, is unknown. In con trast, the 430-nt RNA fragment represents mRNA, which is thought to en code functional aromatase enzyme because its levels are correlated wit h aromatase activity concentrations in preoptic area, hypothalamus, am ygdala, and ovary, Aromatase activity and mRNA levels in the preoptic area and hypothalamus decreased by 7 days after castration and were ma intained at intact levels by treatment with testosterone and dihyhdrot estosterone, but not with estradiol. In contrast, neither aromatase ac tivity nor mRNA levels in the amygdala are affected by castration or h ormone replacement. In addition, sex differences in the regulation of aromatase mRNA were apparent in both the preoptic area and hypothalamu s. These results demonstrate that androgens regulate the transcription or stability of aromatase mRNA in specific brain areas. Moreover, the y suggest that gender differences in androgen responsiveness play an i mportant role in regulating gene expression in the adult rat brain. (C ) 1997 Elsevier Science Inc.