Aromatase distribution and regulation in fish

Abstract

Cytochrome P450 aromatase is the enzyme complex responsible for the synthesis of estrogens by the aromatization of androgens. In the vast majority of tetrapods examined so far, aromatase is the product of the Cyp19 gene, which exists as a single copy per haploid genome. In contrast, in teleosts there are two isoforms of the aromatase gene, Cyp19a and Cyp19b, which encode two structurally different proteins, P450aromA and P450aromB, respectively, with similar catalytic activities. The promoter region of both genes has been characterized in several teleost species and more than 20 different regulatory sites have been identified to date. These include response elements for members of the nuclear receptor superfamily, notably sex steroid receptors, and at least five transcription factors related to neurogenesis. This supports the idea that, besides other functions such as the control of reproduction, aromatase and therefore estrogens are actively involved in neurogenesis. Aromatase mRNA expression studies revealed that P450aromA and P450aromB are preferentially, but not exclusively, expressed in the gonads and brain, respectively. Other organs and tissues where aromatase is expressed, albeit at much lower levels include the pituitary, retina, anterior kidney, testis, liver and visceral fat, suggesting local actions of estrogens in several peripheral targets. Gene expression levels are usually matched by actual catalytic activity, with K (m) usually in the range 5-50 nM and V (max) in the order of a few pmol/mg protein/h. The current challenge is to understand the regulation of both aromatase genes, especially in the context of sex differentiation and as a response to environmental factors, including temperature, social interactions, and endocrine disruptors, which is briefly reviewed. It is also important to gain a better understanding of the specific functions of estrogen in different tissues and key developmental and reproductive events throughout the fish life.