17ƒÒ-estradiol and progesterone regulate anandamide synthesis in the rat uterus

RIBEIRO ML; VERCELLI C; SORDELLI M; FARINA M; CERVINI M; BILLI S; FRANCHI AM

Reproductive Biomedicine on line

Reproductive Healthcare Ltd

Año: 2009 vol. 18 p. 209 - 218

1472-6491

Anandamide is an endocannabinoid known to participate in reproductive processes. In the present work we observed that 17b-estradiol and progesterone modulated the production of anandamide and its metabolizing enzymes in the rat uterus. Anandamide production was highest at the estrous stage and 17b-estradiol and progesterone stimulated its synthesis in ovariectomized rats. During early pregnancy, anandamide production remained constant on days 1 to 5 of gestation and diminished towards day 6. On day 6, implantation sites showed lower synthesis compared to interimplantation sites. In the delayed implantation model, 17b-estradiol inhibited anandamide synthesis compared to progesterone. During pseudopregnancy, anandamide production did not decrease towards day 6 as occurred during normal gestation. The administration of 17b-estradiol augmented anandamide production in rats on day 5 of pseudopregnancy; the treatment with RU-486 did not produce any change in anandamide synthesis. Anandamide metabolizing enzymes were regulated by progesterone and 17b-estradiol. We hypothesized that the effect of ovarian hormones on the synthesis of anandamide depended on different physiologic conditions, estrous cycle and early pregnancy, and on the presence of the activated blastocyst. Thus, ovarian hormones, as signals that emanate from the mother, operate in conjunction with the blastocyst intrinsic program, regulating the synthesis of anandamide in a specific manner during crucial reproductive events that may compromise pregnancy outcome.