Endocrine Abstracts

Introduction

Based upon epidemiological evidence linking hyperthyroidism, inflammation of the ovarian surface and increased risk of ovarian cancer development, we have studied thyroid receptor expression in human ovarian surface epithelial cells (hOSE), and examined the possibility that triiodothyronine (T3) may have direct effects on hOSE cells, the origin of the vast majority of ovarian tumours.

Methods

Human OSE were collected from women undergoing surgery for benign gynaecological conditions, with informed consent and local ethical committee approval. Microarray, post-validated with RT-PCR and immunohistochemistry was used to determine which thyroid hormone receptors were expressed in OSE cells. Primary cultures were treated plus/minus a dose range of T3 (1 and 100 nanomolar), for 24 hours. Quantitative real-time PCR was used to measure gene expression of 11beta hydroxysteroid dehydrogenase type 1 (11bHSDt1), matrix metalloproteinase-9 (MMP-9) and Cyclooxygenase 2 (COX-2), all genes previously demonstrated to be part of the hOSE inflammatory response.

Results

Microarray, RT-PCR and immunohistochemistry demonstrated multiple isoforms of thyroid hormone receptors expressed in hOSE cells. 100 nanomolar T3 increased expression of COX-2 (P<0.01), 11bHSD1 (P<0.01). Both 1 and 100 nanomolar T3 increased MMP-9 expression (P<0.05)

Discussion

We have identified the OSE as a thyroid responsive tissue. Furthermore, the response of OSE cells to T3 mimics that of previously established responses of OSE cells to inflammatory cytokine stimulation in terms of three genes involved in inflammation and tumour development (COX-2, 11bHSD1 and MMP-9). We conclude that T3 may have direct inflammatory effects on the ovarian surface, indicating a potential mechanism to explain the epidemiological links between hyperthyroidism and ovarian cancer.

(Supported by the Medical Research Council Programme grant 0000066).