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.
J Neuroendocrinol. 2008-03-01; 20(3): 335-346
DOI: 10.1111/j.1365-2826.2007.01643.x
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1. J Neuroendocrinol. 2008 Mar;20(3):335-46. doi: 10.1111/j.1365-2826.2007.01643.x.
Epub 2008 Jan 11.
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.
Coyral-Castel S(1), Tosca L, Ferreira G, Jeanpierre E, Rame C, Lomet D, Caraty A,
Monget P, Chabrolle C, Dupont J.
Author information:
(1)Unité de Physiologie de la Reproduction et des Comportements, UMR6175, INRA,
Nouzilly, France.
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 AMPKalpha 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 microg 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.
DOI: 10.1111/j.1365-2826.2007.01643.x
PMID: 18194429 [Indexed for MEDLINE]