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

DE LA VEGA M ; VALLCANERAS S; RAGUSA JA; ARIAS JL; ANZULOVICH AC; CASAIS M

Potrero de los Funes, San Luis República Argentina

Congreso; XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

TNFRp55 deficiency modifies the temporal expression of Bmal1 and Pg metabolizingenzymes in ovary.De la Vega M 1,2 , Vallcaneras S1, Ragusa JA2, Arias JL3, Anzulovich AC2, Casais M1.1LABIR, UNSL. 2LABCRON, 3Lab. Inmul. y Citom. Flujo, IMIBIO-SL, CCT CONICET San Luis. E-mail:magalidlv@hotmail.comWe previously showed that Progesterone (Pg) levels exhibit a circadian rhythm in the corpusluteum. TNF exerts pleiotropic effects through its p55 an p75 receptors. Bmal1 is a keycomponent of the cellular clock machinary. Our objective was to investigate the putative roleof TNF in the modulation of the circadian expression of Bmal1 and two key Pg metabolizingenzymes (3b-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, at 24±2°C, with irradiatedfood and water available ad libitum. Five days before the experiment mice were kept underconstant darkness conditions. Ovaries were isolated every 6 h during a 24h period. Bmal1, 3b-HSD and 20a-HSD transcripts levels were determined by RT-PCR. The expression of Bmal1, 3b-HSD and 20a-HSD genes is circadian in the corpus luteum of wild type animals with maximalexpression 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 thecircadian rhythms. Circadian oscillation of Bmal1 in the corpus luteum would indicate apotencial role of the endogenous clock in the regulation of Pg metabolism. In turn, clockmediatedregulation might be modulated by TNF through its p55 receptor pathway.