Detection of oestrogenic activity of steroids present during mammalian gestation using oestrogen receptor α- and oestrogen receptor β-specific in vitro assays

Abstract

Numerous steroid hormones are present in the foetus but their potential to activate oestrogen receptor (ER) α and/or β is largely unknown. In this study, in vitro assays were developed to rapidly and specifically detect ERα, or ERβ activation by these steroid hormones. Our results showed that several oestrogen precursors and androgens are able to activate both ERα and ERβ. Of special interest is that some of these precursors are able to activate ERα and ERβ at concentrations that are present during human gestation. Moreover, some precursors (dehydroepiandrosterone (DHEA) and 17-hydroxylated pregnenolone sulphate) and androgens (5-androsten-3β,16α,17β-triol and testosterone) showed a more than 100-fold relative preference for ERβ transactivation over ERα transactivation when compared with 17β-oestradiol. Due to their relatively high levels, the precursor steroids DHEA and pregnenolone may be of particular importance in the regulation of ERβ activity in vivo. To obtain information about the oestrogenic activity of the total pool of steroid hormones present during mammalian gestation, steroids were extracted from mouse embryos at different prenatal stages and assayed for oestrogenic activity in the established in vitro assays. Oestrogenic activity was detected in steroid extracts from all stages tested. This study has demonstrated that oestrogen receptor agonists are present in the murine embryo and that oestrogen precursors may contribute to the total pool of agonists during foetal life.