The importance of ERβ signalling in the ovary

This review examines the evidence for a central role of oestrogen receptor beta (ER beta or ESR2 as listed in the MGI Database) in folliculogenesis and hence reproductive biology. Knockout mouse models have been a valuable resource in this respect. The ER beta-null mouse exhibits a granulosa cell phenotype associated with the partial arrest of folliculogenesis and ovulatory dysfunction. Phyto-oestrogens such as genistein, which preferentially activate ER beta, have been shown to alleviate the ovarian phenotype of the oestrogen-depleted aromatase knockout mouse. In normal adult mice, genistein has been shown to cause reproductive defectives following neonatal administration. Studies of ovarian cancer have also informed the literature. A decline in ER beta levels in epithelial ovarian cancers has been hypothesised to be associated with severity of disease and prognosis. Whereas the abundant expression of ER beta in granulosa cell tumours (GCT) of the ovary and evidence that ER beta signalling is transrepressed by the nuclear factor-kappa B pathway in GCT cell lines suggest a pathogenetic role for ER beta in GCT. In recent years, studies into the impact of environmental oestrogens (either in the form of pesticides or plastics) on reproductive function have shown that ER beta-selective toxins cause reproductive dysfunction and impair fertility. It remains to be established as to what genes are regulated by ER beta in the ovary. Finally, ER beta has been shown to be regulated by gonadotrophins, the pituitary hormones mediating ovarian function. Journal of Endocrinology (2010) 205, 15-23