Context: Ovarian surface epithelial (OSE) cells express multiple nuclear hormone receptor genes, including those encoding thyroid hormone (TR) and estrogen (ER) receptors. Ovarian cancer is hormone-dependent and epidemiological evidence links hyperthyroidism, inflammation of the ovarian surface and increased risk of ovarian cancer.

Objective: To assess T3 action on human OSE cells in vitro, asking (1) is there evidence for (pre)receptor control, (2) is T3 inflammatory, and (3) does T3 affect ER expression?

Design: Immunohistochemical analysis of fixed human ovaries and in vitro analysis of human OSE primary cell cultures.

Patients: Twelve women aged 29-50 yr (median 41 yr) undergoing elective gynecological surgery for non-malignant conditions.

Results: Messenger RNA transcripts for TR1, TR2, TRb1 and T3 activating (DIO2) and inactivating (DIO3) deiodinases were present in primary OSE cell cultures by RT-PCR. TR and TR proteins were also localized to intact OSE by immunohistochemistry. Treatment of OSE cell cultures for 24 h with T3 caused dose-dependent mRNA expression of inflammation-associated genes: cyclooxygenase-2 (COX2), matrix metalloproteinase-9 (MMP9) and 11hydroxysteroid dehydrogenase type 1 (11HSD1), determined by quantitative RT-PCR. Finally, treatment with T3 dose-dependently stimulated ER mRNA expression without affecting ER1 or ER2.

Conclusion: The ovarian surface is a potential T3 target. T3 exerts direct inflammatory effects on OSE cell function in vitro. OSE cell responses to T3 include increased expression of ER mRNA, which encodes the ER isoform most strongly associated with ovarian cancer. This could help explain suggested epidemiological links between hyperthyroidism and ovarian cancer.