Skip to Main content Skip to Navigation
Journal articles

The effect of AMP-activated kinase activation on gonadotrophin-releasing hormone secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats

Abstract : Hypothalamic AMP-activated kinase (AMPK) is a key regulator of food intake in mammals. Its role in reproduction at the central level and, more precisely, in gonadotrophin-releasing hormone (GnRH) release has never been investigated. We showed that each subunit of AMPK is present in immortalised GnRH neurones (GT1-7 cells). Treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) and metformin, two activators of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPK alpha atThr172 in GT1-7 cells. Phosphorylation of acetyl-coenzyme A carboxylase at ser79 also increased. Treatment with AICAR (5 mM) or metformin (5 mM) for 4 h inhibited GnRH release in the presence or absence of GnRH (10(-8) M). Specific AMPK inhibitor compound C completely eliminated the effects of AICAR or metformin on GnRH release. Finally, we determined the central effects of AICAR in vivo on food intake and oestrous cyclicity. Ten-week-old female rats received a 50 mu g AICAR or a saline i.c.v. injection. We detected increased AMPK and acetyl-CoA carboxylase phosphorylation, specifically in the hypothalamus, 30 min after AICAR injection. Food intake was significantly higher (P < 0.05) in animals treated with AICAR than in animals injected with saline, 24 h after injection. This effect was abolished after 1 week. Moreover, during the 4 weeks following injection, the interval between two oestrous stages was significantly lower in the AICAR group than in the saline group. Our findings suggest that AMPK activation may act directly at the hypothalamic level to affect fertility by modulating GnRH release and oestrous cyclicity.
Document type :
Journal articles
Complete list of metadata

https://hal.inrae.fr/hal-02666424
Contributor : Migration Prodinra Connect in order to contact the contributor
Submitted on : Sunday, May 31, 2020 - 8:44:11 AM
Last modification on : Tuesday, November 23, 2021 - 5:28:02 PM

Links full text

Identifiers

Collections

Citation

Stéphanie Coyral-Castel, Lucie Tosca, Guillaume Ferreira, Eric Jeanpierre, Christelle Rame, et al.. The effect of AMP-activated kinase activation on gonadotrophin-releasing hormone secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats. Journal of Neuroendocrinology, Wiley, 2008, 20 (3), pp.335-346. ⟨10.1111/j.1365-2826.2007.01643.x⟩. ⟨hal-02666424⟩

Share

Metrics

Record views

57