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J Endocrinol Invest. 2011 Nov;34(10):e362-8. doi: 10.3275/7803. Epub 2011 Jun 21.

Role of the energy sensor adenosine monophosphate-activated protein kinase in the regulation of immature gonadotropin-releasing hormone neuron migration.

Author information

1
Department of Endocrinology, Pathophysiology and Applied Biology, Inter-University Center for Research on Reproductive Health (CIRMAR), Center of Excellence on Neurodegenerative Diseases (CEND), Città Studi University of Milan, Via G. Balzaretti 9, 20133 Milan, Italy.

Abstract

BACKGROUND:

The 5'-AMP-activated protein kinase (AMPK) plays a fundamental role in regulating energy homeostasis as well as feeding and metabolism, through central and peripheral actions. AMPK is activated by conditions causing ATP depletion and by different metabolic molecules, such as adiponectin and AMPK agonist, such as 5-aminoimidazole- 4-carboxamide-1-β-D-ribofuranoside (AICAR). AMPK activation has also been shown to affect the migration of different cell types and to participate in the central control of reproductive function, although information concerning AMPK and the development of the hypothalamic reproductive compartment is lacking.

AIM:

To explore whether AMPK activation by globular adiponectin (gAdipo) and AICAR may affect the migratory ability of GnRH neurons.

MATERIALS AND METHODS:

We used GN11 immature GnRH neurons (in vitro model system), RT-PCR and Western blot analysis, and Boyden's chamber assay.

RESULTS:

gAdipo did not affect FBS-stimulated migration of GN11 cells and activated AMPK through the mandatory phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt, which also interact one to each other. AICAR treatment inhibited FBS-stimulated GN11 cell migration, through a long-lasting activation of AMPK. A downstream activation of ERK1/2 by AICAR was also observed and inhibition of ERK1/2 amplified AICAR-induced inhibition of migration.

CONCLUSIONS:

The direct, but not the indirect, activation of AMPK appears to negatively affect FBSinduced GN11 cell migration, suggesting that the final balance between pro-migratory and anti-migratory actions may also depend upon the specific sequence of intracellular signals activated by one agent.

PMID:
21697647
DOI:
10.3275/7803
[Indexed for MEDLINE]
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