1. Introduction

In 1943, Edward A. Doisy (1893–1986) received the Nobel prize for his discovery of the chemical nature of vitamin K, but Doisy and his colleagues should also be remembered as the discoverers of estriol, estrone and estradiol [1]. Estradiol is a cholesterol derivative mostly known for its actions on the estrus cycle and the maintenance of female sexual characters. Estradiol was originally considered as a female hormone [1], until it was found, unexpectedly at the time, that E2 was present in the urine of the stallion [2]. This finding sets the stage for the discovery that estrogens in fact derive from androgens thanks to the action of cytochrome P450 aromatase, the only enzyme capable of aromatizing the A ring of C19 androgens to convert them into C18 estrogens. With the exception of suidae, in which there are 5 aromatase genes (also named cyp19a1), most vertebrates have a single cyp19a1

gene whose tissue specific expression is driven by multiple aromatase promoters [3]. Apart from the gonads, aromatase is expressed in a large variety of tissues such as the bones, the skin, the adrenals, the adipose tissue, the fetal liver, the placenta and some breast cancers. In addition, aromatase is also well expressed in the central nervous system of all vertebrates where it is supposed to play complex and still poorly understood roles [4–6].

Since the seminal work of Alfred Jost on the hormonal control of sex differentiation in the mammalian fetus [7] and the development of the aromatization hypothesis [8], our views on aromatase and estrogen functions in the brain are largely influenced by the mammalian litera-ture. In rodents, there is considerable evidence that the masculinization effects of testosterone on the organization of male-specific circuits are caused by aromatization and are in fact mediated by estradiol. The molecular and cellular mechanisms underlying those estrogenic effects have been thoroughly studied and involve complex age-, sex- and region-specific actions on cell proliferation, apoptosis and differentiation [9–11]. This provides evidence that, at least in this case, estrogens can modulate neurogenesis to cause irreversible sexual dimorphism of some brain structures. In addition, over the last ten years, a number of studies reported potential effects of estrogens and xeno-estrogens, notably bis-phenol A, in either embryonic neurogenesis and/or in the adult neurogenesis in the hippocampus [12–16]. There has been already several excellent reviews dealing with the putative functions of aromatase in mammals or birds and the role of estrogens in modulating brain functions [11,17–22]. On the other hand, a number of reports have shown that upon mechanical or chemical lesions, there is an up regulation of aromatase expression in either reactive astrocytes surrounding the lesions or in radial glial cells (RGCs) facing the lesions as shown in birds, suggesting that aromatase expression in cells of the astroglial lineage would be part of the mechanisms supporting brain repairs after lesion [11,21,23–28]. Thus aromatase can, under certain circumstances, be expressed in cells of the astrocyte lineage, notably under situation of brain repair, while it is admitted in mammals and birds that aromatase is expressed primarily in neurons [29,30].

In contrast to estradiol, testosterone is usually perceived as a male hormone, but this is not the case in all vertebrates. In fish for example, a wealth of data have demonstrated that testosterone is present in the blood of both males and females [31,32] and that fish have some particular non aromatizable androgens, such as 11-keto-testosterone that is found only in males and triggers male secondary sexual characters and sexual behavior [33]. Fish are also unique in that they exhibit an amazing sexual plasticity. They are the only vertebrates capable of total sex change, either naturally or upon hormonal treatment. Thus, the above-mentioned aromatization hypothesis probably does not apply to teleost fishes, but it is possible that this sexual plasticity is linked to some of the remarkable characteristics of aromatase expression and functions in the brain of teleost fish that will be reviewed in this article.