IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LEYDIG CELL STEROIDOGENESIS: CYCLOOXYGENASE- 2 AND HEME OXYGENASE-1 CROSSTALK
Autor/es:
RAICES T; FRUNGIERI MB; RAICES T; FRUNGIERI MB; BESIO MORENO M; PEREYRA EN; BESIO MORENO M; PEREYRA EN; MATZKIN ME; PIGNATARO OP; MATZKIN ME; PIGNATARO OP
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica, SAIC; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica, SAIC
Resumen:
Heme oxygenase (HO-1) is one of the factors involved intesticular steroidogenesis fine tuning and, as we have previouslydemonstrated, has an inhibitory effect on progesterone (P4) synthesisboth in basal and stimulated (dibutyril cAMP) conditions. Soas to continue with the characterization of this regulatory net work,we aimed to study the involvement of cyclooxygenases (COXs) insteroidogenesis and its interaction with HO-1. Two different tumoralLeydig cell lines were used: MA-10 and R2C. They were treatedwith COX-1 (SC-560) and COX-2 (Meloxicam) selective inhibitorsand hemin, an HO-1 inductor (5 - 20 μM). Protein levels wereanalysed by means of Western Blotting and RIAs were performedto determine P4 concentration. Subcellular localization of COXisoenzymes was assessed using confocal microscopy. Results:COX-1 and COX-2 protein levels were unaffected by the inhibitorsSC-560 and Meloxicam. Besides, they are significantly higherin R2C than in MA-10. COX-1 inhibition did not affect P4 levelsneither in MA-10 nor in R2C. On the contrary, COX-2 inhibitionresulted in an increase in P4 levels in both cell lines. COX-1 andCOX-2 are located in the cytoplasm and nuclear envelope. Theanalysis of the interaction between COX-2 and HO-1 denotes thatin basal conditions in MA-10, 1 μM Meloxicam does not modulatethe inhibitory effect of Hemin on P4 levels. Contrarily, in stimulatedconditions in MA-10, 1 μM Meloxicam partially counteract 20 μMHemin inhibitory effect. In R2C, when Hemin is added together with1 μM Meloxicam, stimulation with this inhibitor is reverted almostto control values. Additionally, Meloxicam increases HO-1 proteinlevels beyond hemin stimulation in a concentration-dependentmanner. In conclusion, the results suggest that COX-2 and HO-1interact in the cross-regulation of testicular steroidogenesis andHO-1 protein levels.