Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis.

Rae, Mick T; Niven, D; Ross, A; Forster, T; Lathe, R; Critchley, Hilary O D; Ghazal, P; Hillier, Stephen G

Abstract

The human ovarian surface epithelium (HOSE) is a common site of gynaecological disease including endometriosis and ovarian cancer, probably due to serial injury-repair events associated with successive ovulations. To comprehend the importance of steroid signalling in the regulation of the HOSE, we used a custom microarray to catalogue the expression of over 250 genes involved in the synthesis and reception of steroid hormones, sterols and retinoids. The array included a subset of non-steroidogenic genes commonly involved in pro-/anti-inflammatory signalling. HOSE cells donated by five patients undergoing surgery for non-malignant gynaecological conditions were cultured for 48 h in the presence and absence of 500 pg/ml interleukin-1alpha (IL-1alpha). Total RNA was reverse-transcribed into biotin-labelled cDNA, which was hybridised to the array and visualised by gold-particle resonance light scattering and charge-coupled device (CCD) camera detection. Results for selected genes were verified by quantitative reverse-transcription PCR. In five out of five cases, untreated HOSE cells expressed genes encoding enzymes required for de novo biosynthesis of cholesterol from acetate and subsequent formation of C21-pregnane and C19-androstane steroids. Consistent with the inability of HOSE cells to synthesise glucocorticoids, oestrogens or 5alpha-reduced androgens de novo, CYP21, CYP19 and 5alpha-reductase were not detected. The only steroidogenic gene significantly up-regulated by IL-1alpha was 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1). Other cytokine-induced genes were IL-6, IL-8, nuclear factor kappaB (NFkappaB) inhibitor alpha, metallothionein-IIA and lysyl oxidase: inflammation-associated genes that respond to glucocorticoids. The only steroidogenic gene significantly suppressed by IL-1alpha was 3betaHSD1. Other genes suppressed by IL-1alpha were aldehyde dehydrogenase (ALDH) 1, ALDH 10, gonadotrophin hormone-releasing hormone receptor, peroxisome proliferation-activated receptor-binding protein (PPAR-bp) and nuclear receptor subfamily 2 group F member 2. These results define a steroidogenic phenotype of cultured HOSE cells and provide a limited expression profile for genes with associated signalling functions. IL-1alpha co-ordinately induces 11betaHSD1 and a panel of glucocorticoid-regulated, inflammation-associated genes in HOSE cells, providing further evidence that cortisol generated by 11betaHSD1 could participate in the local resolution of inflammation associated with ovulation.

Citation

Rae, M. T., Niven, D., Ross, A., Forster, T., Lathe, R., Critchley, H. O. D., Ghazal, P., & Hillier, S. G. (2004). Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis. Journal of Endocrinology, 183, 19-28. https://doi.org/10.1677/joe.1.05754

• Journal Article Type: Article
• Publication Date: Oct 1, 2004
• Deposit Date: Jun 30, 2008
• Print ISSN: 0022-0795
• Electronic ISSN: 1479-6805
• Publisher: BioScientifica
• Peer Reviewed: Peer Reviewed
• Volume: 183
• Pages: 19-28
• DOI: https://doi.org/10.1677/joe.1.05754
• Keywords: human ovarian surface epithelium; endometriosis; ovarian cancer; steroid signalling; interleukin-1alpha
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/1662
• Publisher URL: http://dx.doi.org/10.1677/joe.1.05754