A new aspect of the pharmacological and physiological significance of the aromatase/estrogen system

Abstract

Aromatase (estrogen synthetase) catalyzes a key step in estrogen biosynthesis and plays an important role in reproductive processes in the ovary and placenta. In this context, aromatase is an enzyme producing estrogen as an endocrine female sex hormone. Recently, it has reported that aromatase is also present in various extra-gonadal tissues and is tissue-specifically regulated by various factors. This tissue-specific regulation of human aromatase gene is realized by alternative utilization of multiple exon 1's; exons 1a, 1b, 1c, 1d, 1e, and 1f that are specific for expression in the placenta, skin fibroblasts/fetal liver, ovary, ovary/prostate/testis, placenta, and brain, respectively. Each of the tissue-specific exon 1's is flanked by a unique promoter containing basic and regulatory elements. The facts that (i) aromatase is distributed in various gonadal and extra-gonadal tissues and (ii) regulated tissue-specifically by various factors, (iii) estrogen participates in specific physiological functions of various tissues, and (iv) estrogen receptor is also distributed in various tissues strongly indicate that estrogen locally produced by aromatase acts in various tissues as a multi-functional paracrine or autocrine hormone. This idea was discussed in connection with the Kd value for the estrogen receptor and serum concentration of estrogen.