TNFRp55 deficiency modifies the temporal expression of Bmal1 and Pg metabolizing enzymes in ovary.

DE LA VEGA MAGALÍ; VALLCANERAS SANDRA; RAGUSA JOSÉ ANTONIO; ARIAS JOSÉ LUIS; ANZULOVICH ANA CECILIA; CASAIS MARILINA

POTRERO DE LOS FUNES, SAN LUIS.

Congreso; 47º REUNION ANUAL SOCIEDAD ARGENTINA DE INVESTIGACION EN BIOQUIMICA Y BIOLOGIA MOLECULAR; 2011

SOCIEDAD ARGENTINA DE INVESTIGACION EN BIOQUIMICA Y BIOLOGIA MOLECULAR

We previously showed that Progesterone (Pg) levels exhibit a circadian rhythm in the corpus luteum. TNF exerts pleiotropic effects through its p55 an p75 receptors. Bmal1 is a key component of the cellular clock machinary. Our objective was to investigate the putative role of TNF in the modulation of the circadian expression of Bmal1 and two key Pg metabolizing enzymes (3-HSD and 20-HSD) in C57BL/6, wild type and TNFRp55-/- mice, in the diestrus stage. Animals were maintained on a 12-h light: 12-h dark cycle, at 24±2°C, with irradiated food and water available ad libitum. Five days before the experiment mice were kept under constant darkness conditions. Ovaries were isolated every 6 h during a 24h period. Bmal1, 3-HSD and 20-HSD transcripts levels were determined by RT-PCR. The expression of Bmal1, 3-HSD and 20-HSD genes is circadian in the corpus luteum of wild type animals with maximal expression peaks occurring at CT 05:04±00:41, 18:27±00:04 and 19:15±02:18, respectively. TNFRp55 deficiency significantly increased the amplitude and modified the phase of the circadian rhythms. Circadian oscillation of Bmal1 in the corpus luteum would indicate a potencial role of the endogenous clock in the regulation of Pg metabolism. In turn, clock-mediated regulation might be modulated by TNF through its p55 receptor pathway.