Figure 5

Model for the role of oestrogen and the gonadal determination pathway. In normal XY gonads, the somatic cells upregulate SRY, which in turn upregulates SOX9. SOX9 can then translocate to the nucleus and activate the expression of AMH to ensure normal male urogenital development. In the presence of oestrogen, the bipotential somatic cell is instead directed into the granulosa cell pathway. SRY fails to upregulate, and any SOX9 protein produced fails to enter the nucleus. In the absence of nuclear SOX9, AMH fails to upregulate and ovarian genes (FOXL2 and WNT4) are activated. Exogenous oestrogen therefore has the ability to direct XY bipotential somatic cells to a granulosa cell fate. Oestrogen may act in a similar manner to maintain granulosa cell fate in mature eutherian ovaries, preventing basal levels of SOX9 protein from translocating to the nucleus and propagating its own upregulation.