TNFRp55 DEFICIENCY MODIFIES THE TEMPORAL EXPRESSION OF BMAL1 AND PG METABOLIZING ENZYMES IN OVARY

DE LA VEGA M; VALLCANERAS SS; RAGUSSA V; ARIAS JL; ANZULOVICH AC; CASAIS M

Potrero de los Funes, San Luis

Congreso; 47th. Annual meeting SAIB; 2011

SAIB

We previously showed that Progesterone (Pg) levels exhibit acircadian rhythm in the corpus luteum. TNF exerts pleiotropiceffects through its p55 and p75 receptors. Bmal1 is a key componentof the cellular clock machinery. Our objective was to investigate theputative role of TNF in the modulation of the circadian expression ofBmal1 and two key Pg metabolizing enzymes (3ß-HSD and 20a-HSD) in C57BL/6, wild type and TNFRp55-/- mice, in the diestrusstage. Animals were maintained on a 12-h light: 12-h dark cycle, at24±2°C, with irradiated food and water available ad libitum. Fivedays before the experiment mice were kept under constant darknessconditions. Ovaries were isolated every 6 h during a 24h period.Bmal1, 3ß-HSD and 20a-HSD transcripts levels were determinedby RT-PCR. The expression of Bmal1, 3ß-HSD and 20a-HSD genesis circadian in the corpus luteum of wild type animals with maximalexpression peaks occurring at CT 05:04±00:41, 18:27±00:04 and19:15±02:18, respectively. TNFRp55 deficiency significantlyincreased the amplitude and modified the phase of the circadianrhythms. Circadian oscillation of Bmal1 in the corpus luteum wouldindicate a potential role of the endogenous clock in the regulation ofPg metabolism. In turn, clock-mediated regulation might bemodulated by TNF through its p55 receptor pathway.