Effects of Cox-2 Inhibitors and Translocator Protein Drug Ligands on Progesterone Production by Mouse Leydig Tumor Cells

Cyclooxygenase 2 (COX-2) inhibitors and translocator protein 18 kDa (TSPO) drug ligands have been shown to have stimulatory effects on steroid production. Given that their mechanisms of action differ, we hypothesized that a combination treatment of both TSPO drug ligands and COX-2 inhibitors might have additive or synergistic effects on steroid production in the Leydig cell. We tested the effects of each of four COX-2 inhibitors (Apigenin, DFU, NS398, Indomethacin) and two TSPO drug ligands (Ro5, FGIN) on steroid hormone (progesterone) production by MA-10 mouse Leydig tumor cells. The four COX-2 inhibitors had similar effects across all concentrations when inhibitor-treated cells were then incubated with luteinizing hormone (LH). When cells were treated with the COX-2 inhibitor and then incubated with dibutyryl cAMP (dbcAMP), dose-response effects were seen. DFU and Indo were the two COX-2 inhibitors that had maximal effects on mean progesterone production. Treatment of cells with the TSPO drug ligands, Ro5 and FGIN, also resulted in increased progesterone production. However, we found no additive or synergistic effects of TSPO ligands and COX-2 inhibitors when cells were treated in the presence of LH or dbcAMP. Thus, although the mechanisms by which COX-2 inhibitors and TSPO drug ligands stimulate steroid formation differ, treatment of cells by combining the two classes of compounds had no greater effect on progesterone production than either alone. As yet, however, the possibility that these compounds could have additive or synergistic effects has not been assessed using primary cells or in vivo. Thesis Readers: Dr. Barry Zirkin (Advisor) and Dr. Terry Brown