Endocrine Abstracts

The gene FOXL2 encodes a forkhead transcription factor whose mutations or misregulation are responsible for the blepharophimosis-ptosis-epicanthus inversus (BPES) syndrome and more recently have been associated with ovarian granulosa cell tumors (OGCT). BPES is a genetic disorder involving craniofacial abnormalities associated with premature ovarian failure. OGCTs are endocrine malignancies, accounting for up to 5% of ovarian cancers, the treatment of which is challenging. I will summarize recent data on FOXL2 transcriptional targets and molecular partners, its post-translational modifications, its mutations and its involvement in OGCTs. In the ovarian context, FOXL2 is involved in the regulation of cholesterol and steroid metabolism, apoptosis, reactive oxygen species detoxification and cell proliferation. In addition, one of the main roles of FOXL2 is to preserve the identity of ovarian granulosa cells even at the adult stage and to prevent their transdifferentiation into Sertoli-like cells. These recent advances indicate that FOXL2 is a key factor for ovarian development and maintenance. The elucidation of the impact of FOXL2 germline and somatic mutations will ensure a better understanding of the pathogenesis of BPES and of OGCTs.