5 AMP-activated protein kinase (AMPK) is a serine/threonine kinase that acts as a fuel gauge in regulating energy metabolism by switching on catabolic pathways and switching off anabolic pathways. A role for AMPK in reproductive functions has recently emerged. We have showed that AMPK is expressed in granulosa cells and cumulus-oocyte complexes (COCs) in the ovary of several species (rat, cow and women). In vitro, pharmacological activation of AMPK by AICAR or metformin, two known activators of AMPK, reduced progesterone and/or [oelig]stradiol secretion in granulosa cells of these species. These effects are mediated through a regulation of the steroidogenic enzyme 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase) expression and the Mitogen-activated protein kinase ERK1/2 signaling pathway. Moreover, AMPK might directly regulate oocyte maturation in different species. These studies suggest a role for AMPK in female fertility through a direct action at the ovary level. However, AMPK is also present in the nervous system central and particularly in the hypothalamus. Thus, we have recently investigated the role of this kinase in the central regulation of female reproduction. We have first determined the effect of one intracerebroventricular (i.c.v) injection of AICAR on the oestrous cyclicity in rat. Injection of AICAR i.c.v specifically increased hypothalamic AMPK activation and reduced the interval between two oestrous stages in vivo. We have also examined the effects of metformin and AICAR on GnRH secretion in immortalized GnRH neurones (GT1-7 cells). We have demonstrated that treatment with either metformin or AICAR significantly inhibits GnRH release in the presence and absence of GnRH in GT1-7 cells. Furthermore, these effects were abolished by the specific AMPK inhibitor compound C, suggesting that AMPK is involved in metformin- and AICAR-induced inhibition of GnRH release. Taken together, our findings suggest a role for AMPK in the ovarian and central regulation of female reproduction.