The immunocytochemical expression of the inhibin/activin subunits in normal human endometrium and the upregulation in interferon-ß1a-stimulated cells of the Ishikawa cell line

Introduction: Inhibins consist of an α- and one ß-subunit (A or B). They have substantial function in reproduction and seem to play a role in tumor development. Aims of this study were (a) to analyse inhibin/activin- subunit-expression in isolated glandular epithelial cells of normal human endometrium and (b) to determine expression changes of these subunits in endometrial Ishikawa carcinoma cell line after stimulation with interferon-ß1a. Materials and Methods: Normal endometrium was obtained from women who underwent hysterectomy. After adding interferon-ß1a (1000IE/ml) for 48h to confluent-cultured Ishikawa cells, these were analyzed for α-, ßA- and ßB-subunit. The expression was detected by immunocytochemistry and –fluorescence and was analyzed with a semi-quantitative score. Results: Glandular cells express Inh-α, -βA and -βB. After cultivation, expression of Inh-α and Inh-βB was downregulated, whereas Inh bA-expression remained high. We showed a simultaneous α- and βA-, as well as α- and βB-expression. Inh-α could not be detected in unstimulated Ishikawa-cells, while it was significantly up regulated in interferon-stimulated cells (p<0.02). Inh-ßA and -ßB were primarily observed in mitotic unstimulated cells. After stimulation, their expression was higher (p<0.05 each), and was observed also in non-mitotic cells. Discussion: Expression of all inhibin subunits was shown in isolated endometrial epithelial cells. Downregulation of inh-α and -βB during cultivation in culture medium without hormones suggests a hormone dependency of Inhibin expression. Additionally, we demonstrated for the first time a relationship between interferon and inhibin subunits. Expression of all subunits was significantly up regulated in the Ishikawa cells after interferon-ß1a-stimulation. Since Inh-α is thought to be tumor suppressive in ovarian cancer in the mouse model, interferon might activate this gene. If this effect can be used as therapeutic options, remains to be clarified.