“Effects of dehydroepiandrosterone and metformin in corpus luteum regression”

MOTTA AB; SANDER V; PIEHL L; FACORRO G; RUBIN DE CELLIS E

San Francisco

Congreso; 6th Annual Meeting of the Androgen Excess and PCOS Society, Fertility and Sterility; 2008

Androgen Excess and PCOS Society, Fertility and Sterility

EFFECT OF DEHYDROEPIANDROSTERONE AND METFORMIN IN CORPUS LUTEUM REGRESSION. Motta AB(1), Sander VA(1), Facorro G(2), Piehl L(2), Rubin de Celis E(2) (1)Laboratorio de Fisio-patología Ovárica, CEFYBO-UBA,CONICET-Buenos Aires, Argentina; and (2)Dept. of Física, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina Hyperandrogenism alters ovarian function leading to an abnormal length of estrus cycles, anovulation and high rates of recurrent miscarriages. The aim of the present study was to investigate the action of androgens on corpus luteum (CL) regression and the mechanism by which N, N- dimethylbiguanide metformin restores cyclicity. The injection of dehydroepiandrosterone (DHEA; 60 mg/Kg body weight) to BALB/c mice 24 and 48 hours before luteolysis increased serum progesterone and estradiol levels and decreased ovarian oxidative stress (since DHEA decreased ovarian lipid peroxidation and increased superoxide dismutase and catalase activities). Therefore, the treatment with DHEA diminished the ovarian production of the luteolytic prostaglandin (PG) F2 alpha and increased both the ovarian levels of the luteotrophic PGE and the ovarian nitrite concentration. We also found that the effects of DHEA on NO production involved the regulation of the corresponding main enzymes of this pathway. Metformin prevented the action of DHEA on ovarian oxidative stress, progesterone levels, PGs production and NO levels also involving the corresponding enzymes. We conclude that hyperandrogenism is able to delay the luteolytic process. This observation could explain, in part, the abnormal length of the sexual cycle of women with PCOS. We also reported novel mechanisms by which metformin is able to act as an anti-inflammatory and antioxidant drug during the processes of hyperandrogenism. (supported in part by ANPCyT grants PICTR 32529 and PICT 949).