Mechanisms in tissue-specific regulation of estrogen biosynthesis in humans.

ABSTRACT

In humans, aromatase P450, which catalyses conversion of C(19)-steroids to estrogens, is expressed in several tissues, including gonads, brain, adipose tissue, skin and placenta, and is encoded by a single-copy gene (CYP19); however, this does not hold true for all species. The human gene is approximately 130 kb and its expression is regulated, in part, by tissue-specific promoters and by alternative splicing mechanisms. Using transgenic mouse technology, it was observed that ovary-, adipose tissue- and placenta-specific expression of human CYP19 is directed by relatively small segments of DNA within 500 bp upstream of each of the tissue-specific first exons. Thus, the use of alternative promoters allows greater versatility in tissue-specific regulation of CYP19 expression. Characterization and identification of transcription factors and crucial cis-acting elements within genomic regions that direct tissue-specific expression will contribute to improved understanding of the regulation of CYP19 expression in the tissues that synthesize estrogens under both physiological and pathophysiological conditions.