Epigenetic regulation of Progesterone Receptor isoforms: From classical models to the sexual brain

Progesterone Receptor is a member of the nuclear receptor superfamily, which regulates several functions in both reproductive and non-reproductive tissues. Progesterone Receptor gene encodes for two main isoforms, A and B, and contains two specific promoters with their respective transcription start sites. The mRNA expression of both isoforms is mainly regulated by estrogens and specifically via the Estrogen Receptor Alpha, in a context specific manner. Furthermore, it has been reported in extensive physiological and pathological models that Progesterone Receptor isoforms regulation is related to the epigenetic state of their respective promoters. Epigenetic regulation of Progesterone Receptor isoforms in the brain is a recent and scarcely explored field in neurosciences. This review focuses on the epigenetic mechanisms involved in Progesterone Receptor regulation, emphasizing the implications for the sexual brain. Future directions for research about this important field are also discussed.