Authors: Elia, E.; Sander, V.; Luchetti, C.G.; Solano, M.E.; Di Girolamo, G.; Gonzalez, C.; Motta, A.B.

Source: Molecular Human Reproduction, Volume 12, Number 8, August 2006 , pp. 475-481(7)

Publisher: Oxford University Press

Abstract:

The aim of this study was to investigate the mechanisms by which N,N′-dimethylbiguanide metformin (50 mg/100 g body weight (BW) in 0.05 ml of water, given orally with a cannula) prevents the ovarian disorders provoked by the hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c mice. The injection of DHEA (6 mg/100 g BW in 0.1 ml of oil) for 20 consecutive days re-creates a mouse model that resembles some aspects of the human polycystic ovary syndrome (PCOS). The treatment with DHEA increased ovarian oxidative stress because it enhanced lipid peroxidation (LPO) and diminished both catalase (CAT) activity and glutathione (GSH) content. Therefore, the treatment with DHEA diminished both ovarian nitric oxide synthase (NOS) activity and prostaglandin E (PGE) production. When metformin was administered together with DHEA, the ovarian GSH content, NOS activity and PGE production did not differ when compared with controls. However, metformin was not able to prevent the effect of DHEA on ovarian LPO or CAT activity. Finally, DHEA increased the ovarian protein expressions of inducible NOS (iNOS), inducible cyclooxygenase (COX2) and the phosphorylated AMP-depen-dent kinase α (AMPK-α) (Thr172). Metformin administered together with DHEA was able to prevent the increase of ovarian iNOS and COX2 expressions and to enhance the activation of phosphorylated AMPK-α expression.

Keywords: AMP-dependent kinase α; cyclooxygenase; dehydroepiandrosterone; polycystic ovary syndrome

Document Type: Research article

DOI: http://dx.doi.org/10.1093/molehr/gal057

Publication date: 2006-08-01

More about this publication?

• Molecular Human Reproduction publishes articles on the molecular aspects of human reproductive physiology and pathology, endocrinology, andrology,gonadal function, gametogenesis, fertilization, embryo development, implantation, pregnancy and contraception. Reproductive genetics is also an important part of Molecular Human Reproduction. Studies on animal models are welcome as long as a clear relevance to human reproduction can be shown. Published papers include peer-reviewed original research reports, short review articles and commentaries. Molecular Human Reproduction is published on behalf of the European Society of Human Reproduction and Embryology.

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