| First Author | Gegenhuber B | Year | 2022 |
| Journal | Nature | Volume | 606 |
| Issue | 7912 | Pages | 153-159 |
| PubMed ID | 35508660 | Mgi Jnum | J:338096 |
| Mgi Id | MGI:7367090 | Doi | 10.1038/s41586-022-04686-1 |
| Citation | Gegenhuber B, et al. (2022) Gene regulation by gonadal hormone receptors underlies brain sex differences. Nature 606(7912):153-159 |
| abstractText | Oestradiol establishes neural sex differences in many vertebrates(1-3) and modulates mood, behaviour and energy balance in adulthood(4-8). In the canonical pathway, oestradiol exerts its effects through the transcription factor oestrogen receptor-alpha (ERalpha)(9). Although ERalpha has been extensively characterized in breast cancer, the neuronal targets of ERalpha, and their involvement in brain sex differences, remain largely unknown. Here we generate a comprehensive map of genomic ERalpha-binding sites in a sexually dimorphic neural circuit that mediates social behaviours. We conclude that ERalpha orchestrates sexual differentiation of the mouse brain through two mechanisms: establishing two male-biased neuron types and activating a sustained male-biased gene expression program. Collectively, our findings reveal that sex differences in gene expression are defined by hormonal activation of neuronal steroid receptors. The molecular targets we identify may underlie the effects of oestradiol on brain development, behaviour and disease. |
