ABSTRACT
Physiological estrogens are formed from androgenic steroids by the action of the enzyme aromatase, which is a member of the cytochrome P450 superfamily, and encoded by the CYP19 gene. In humans, aromatase expression and hence estrogen biosynthesis occurs in a number of tissue sites including ovary, placenta, fetal liver, adipose, bone and brain. Tissuespecific expression is regulated by tissue-specific promoters which are located upstream of a number of untranslated first exons which are incorporated into the transcripts by alternative splicing. Analysis of the phenotypes of humans with natural mutations of the aromatase gene, as well as mice in which the gene has been inactivated by targeted disruption, have revealed a number of new and unexpected roles for estrogens in both males and females. These include roles in bone mineralization, lipid and carbohydrate metabolism, and spermatogenesis in the male. This latter role questions the very definition of the term “estrogen”, at least in mice, since in this limited context, estradiol should more properly be considered androgenic. This review will briefly summarise the present and sometimes contradictory state of knowledge regarding the diverse roles which are played by the products of the aromatase reaction, and point to future directions which may help to clarify these issues.
