Oestrogens and temperature-dependent sex determination in reptiles: all is in the gonads.

In many species of oviparous reptiles, the first steps of gonadal sex differentiation depend on the incubation temperature of the eggs. Feminization of gonads by exogenous oestrogens at a male-producing temperature and masculinization of gonads by antioestrogens and aromatase inhibitors at a female-producing temperature have irrefutably demonstrated the involvement of oestrogens in ovarian differentiation. Nevertheless, several studies performed on the entire gonad/adrenal/mesonephros complex failed to find differences between male- and female-producing temperatures in oestrogen content, aromatase activity and aromatase gene expression during the thermosensitive period for sex determination. Thus, the key role of aromatase and oestrogens in the first steps of ovarian differentiation has been questioned, and extragonadal organs or tissues, such as adrenal, mesonephros, brain or yolk, were considered as possible targets of temperature and sources of the oestrogens acting on gonadal sex differentiation. In disagreement with this view, experiments and assays carried out on the gonads alone, i.e. separated from the adrenal/mesonephros, provide evidence that the gonads themselves respond to temperature shifts by modifying their sexual differentiation and are the site of aromatase activity and oestrogen synthesis during the thermosensitive period. Oestrogens act locally on both the cortical and the medullary part of the gonad to direct ovarian differentiation. We have concluded that there is no objective reason to search for the implication of other organs in the phenomenon of temperature-dependent sex determination in reptiles. From the comparison with data obtained in other vertebrates, we propose two main directions for future research: to examine how transcription of the aromatase gene is regulated and to identify molecular and cellular targets of oestrogens in gonads during sex differentiation, in species with strict genotypic sex determination and species with temperature-dependent sex determination.