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

Rae, Mick, Niven, D, Ross, A, Forster, T, Lathe, R, Critchley, H O, Ghazal, P and 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 (1). pp. 19-28. ISSN 0022 0795

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Abstract/Description

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.

Item Type: Article
Print ISSN: 0022 0795
Electronic ISSN: 1479-6805
Uncontrolled Keywords: human ovarian surface epithelium; endometriosis; ovarian cancer; steroid signalling; interleukin-1alpha;
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Life Sciences
Dewey Decimal Subjects: 500 Science > 570 Life sciences; biology > 572 Biochemistry
600 Technology > 610 Medicine & health > 618 Gynecology, obstetrics, pediatrics & geriatrics
600 Technology > 610 Medicine & health > 611 Human anatomy, cytology & histology
Library of Congress Subjects: R Medicine > RG Gynecology and obstetrics
Q Science > QP Physiology
Item ID: 1662
Depositing User: RAE Import
Date Deposited: 30 Jun 2008 11:36
Last Modified: 09 May 2013 16:43
URI: http://researchrepository.napier.ac.uk/id/eprint/1662

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