Endocrine Abstracts

At least 90% of human ovarian cancers originate in the OSE. Most studies indicate that EOC is oestrogen responsive. Paradoxically, ovarian cancer generally occurs after the menopause, which raises the question if oestrogen is involved, where does it come from? We hypothesise that the high circulating concentrations of conjugated (inactive) oestrogens in post-menopausal women are substrates for formation of active oestrogen in the OSE through the hydrolytic enzyme activity of Steroid Sulphatase (STS). We previously showed that the presence of STS in normal OSE cells and now confirm this by immunohistochemistry and investigate its presence and regulation in EOC, OSE and ovarian cancer cell lines.

Normal ovaries, OSE and ovarian tumours were collected with consent and local Ethical Committee approval from women undergoing surgical procedures. STS was detected in paraffin-embedded tissue sections using a rabbit polyclonal antibody against human STS. SKOV-3 and PEO-14 cancer cell lines, primary ovarian cancer cells and normal OSE were cultured for 48 h in the presence or absence of inflammatory cytokines. mRNA was extracted and transcribed cDNA was analysed for expression of oestrogen receptor (ER) α, ERβ and STS gene expression using pre-validated reagents for Q-RTPCR.

Immunohistochemistry confirmed the presence of STS protein in normal OSE (3/3) and EOC (3/3). SKOV-3 cells expressed the highest level of ERα and STS mRNA, whereas ERβ was barely detectable. IL-1α was the most stimulatory cytokine and enhanced STS expression 2-fold.

These results confirm that STS and ERα are expressed in normal OSE and EOC and that SKOV-3 cells respond to inflammatory cytokines with an increase in STS mRNA. We therefore see evidence for a potential mechanism whereby circulating conjugated oestrogens could be converted locally to active oestrogen not only in normal OSE in post-menopausal women, but also in EOC.