Progesterone modulates endocannabinoid and nitrergic systems of peripheral lymphocytes.

FRANCHI AM; WOLFSON ML; AISEMBERG J; VERCELLI CA

Palm Cove, Queensland, Australia

Congreso; XI International Congress of Reproductive Immunology.; 2010

Anandamide (AEA) is an endocannabinoid necessary for the implantation, but its synthesis exacerbated and / or decreased metabolism is related to early abortions in women. LPS induces AEA synthesis in murine macrophages and also inhibits the activity of the enzyme that degrades AEA (fatty acid amidohydrolase, FAAH). Nitric oxide (NO) is an essential molecule during pregnancy, but large quantities can cause septic embryonic resorption (ER). Previous studies from our laboratory indicate that LPS causes ER in mice with an increase in the production of NO. Progesterone (P) serum levels were diminished in these animals and this hormone abrogated the augmentation of uterine and decidual synthesis of PGE, NO and TNFa  due to LPS. The aim of this work was to study if P modulates endocannabinoid and nitrergic system in murine peripheral lymphocytes. Peripheral lymphocytes from pregnant mice had higher activity of FAAH than those from non pregnant animals (NP). In NP mice, our results show that treatment with LPS decreases both the activity and the expression of FAAH, and that P reverses the effects of the endotoxin.    We observed that LPS increases the production of NO and the expression of inducible NO synthase in lymphocytes, a fact which is reversed by treatment with P. These results suggest that P, which is elevated in pregnancy, may have a protective effect on inflammatory processes mediated by NO and AEA in murine lymphocytes. All the protective effects of P could be abolished by the treatment with two P antagonist: RU-486 and lonaprizan. So we studied the expression of P receptor and we detected the expression of PRA and PRB and its modulation by LPS and P. Several inflammatory molecules could participate in the mechanism of LPS-induced resorption and their modulation by P could be a useful tool to prevent early pregnancy loss.