Gonadotropin-releasing hormone-expressing neurons immortalized conditionally are activated by insulin: implication of the mitogen-activated protein kinase pathway

Details

Serval ID
serval:BIB_CD18723C29F5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gonadotropin-releasing hormone-expressing neurons immortalized conditionally are activated by insulin: implication of the mitogen-activated protein kinase pathway
Journal
Endocrinology
Author(s)
Salvi  R., Castillo  E., Voirol  M. J., Glauser  M., Rey  J. P., Gaillard  R. C., Vollenweider  P., Pralong  F. P.
ISSN
0013-7227 (Print)
Publication state
Published
Issued date
02/2006
Volume
147
Number
2
Pages
816-26
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Abstract
Energy balance exerts a critical influence on reproduction via changes in the circulating levels of hormones such as insulin. This modulation of the neuroendocrine reproductive axis ultimately involves variations in the activity of hypothalamic neurons expressing GnRH. Here we studied the effects of insulin in primary hypothalamic cell cultures as well as a GnRH neuronal cell line that we generated by conditional immortalization of adult hypothalamic neurons. These cells, which represent the first successful conditional immortalization of GnRH neurons, retain many of their mature phenotypic characteristics. In addition, we show that they express the insulin receptor. Consistently, their stimulation with insulin activates both the phosphatidylinositol 3-kinase and the Erk1/2 MAPK signaling pathways and stimulates a rapid increase in the expression of c-fos, demonstrating their responsiveness to this hormone. Further work performed in parallel in immortalized GnRH-expressing cells and primary neuronal cultures containing non-GnRH-expressing neurons shows that insulin induces the expression of GnRH in both models. In primary cultures, inhibition of the Erk1/2 pathway abolishes the stimulation of GnRH expression by insulin, whereas blockade of the phosphatidylinositol 3-kinase pathway has no effect. In conclusion, these data strongly suggest that GnRH neurons are directly sensitive to insulin and implicate for the first time the MAPK Erk1/2 signaling pathway in the central effects of insulin on the neuroendocrine reproductive axis.
Keywords
Animals Cell Culture Techniques/methods Cell Line Clone Cells Energy Metabolism/*physiology Female Gene Expression Profiling Gonadotropin-Releasing Hormone/*metabolism Hypothalamus/cytology/*metabolism Insulin/pharmacology/*physiology Mitogen-Activated Protein Kinases/*metabolism Neurons/cytology/*metabolism Phenotype Rats Second Messenger Systems/physiology Signal Transduction/physiology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:06
Last modification date
20/08/2019 15:47
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