The present review focuses on the roles of estrogens and aromatase (Cyp19a1a), the
enzyme needed for their synthesis, in fish gonadal sex differentiation. Based on the
recent literature, we extend the already well accepted hypothesis of an implication
of estrogens and Cyp19a1a in ovarian differentiation to a broader hypothesis that
would place estrogens and Cyp19a1a in a pivotal position to control not only ovarian,
but also testicular differentiation, in both gonochoristic and hermaphrodite fish
species. This working hypothesis states that cyp19a1a up-regulation is needed not
only for triggering but also for maintaining ovarian differentiation and that cyp19a1a
down-regulation is the only necessary step for inducing a testicular differentiation
pathway. When considering arguments for and against, most of the information available
for fish supports this hypothesis since either suppression of cyp19a1a gene expression,
inhibition of Cyp19a1a enzymatic activity, or blockage of estrogen receptivity are
invariably associated with masculinization. This is also consistent with reports on
normal gonadal differentiation, and steroid-modulated masculinization with either
androgens, aromatase inhibitors or estrogen receptor antagonists, temperature-induced
masculinization and protogynous sex change in hermaphrodite species. Concerning the
regulation of fish cyp19a1a during gonadal differentiation, the transcription factor
foxl2 has been characterized as an ovarian specific upstream regulator of a cyp19a1a
promoter that would co-activate cyp19a1a expression, along with some additional partners
such as nr5a1 (sf1) or cAMP. In contrast, upstream factors potentially down-regulating
cyp19a1a during testicular differentiation are still hypothetical, such as the dmrt1
gene, but their definitive characterization as testicular repressors of cyp19a1a would
strongly strengthen the hypothesis that early testicular differentiation would need
active repression of cyp19a1a expression.
Copyright 2009 Elsevier Inc. All rights reserved.