Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain.

Aromatase in the brain is supposed to participate in sexual differentiation of the brain. The presence of a brain-specific exon 1 and promoter in the human aromatase gene was examined in the 5' regions of aromatase cDNAs isolated from the amygdala and hypothalamus areas. The DNA sequences of all the isolated clones were different in the 5' regions encoded by exon 1 from those encoded by any alternative exons 1 of human aromatase gene. This unique sequence was also found in the clones isolated from a human genomic library and indicated to be that of a new exon 1. It involved putative TATA and CAAT boxes, Ad4 sequence, and the androgen responsive element in the promoter region. Reverse transcriptase-polymerase chain reaction analysis of mRNAs in various tissues revealed that expression of this unique species of aromatase mRNA is specific for the brain, in particular in the fetal brain. These show that the aromatase gene in the human brain is expressed by means of the brain-specific exon 1 and promoter, and may be responsible for sexual differentiation of the brain in the fetal period.