Control of GnRH neuronal activity by metabolic factors: the role of leptin and insulin

Details

Serval ID
serval:BIB_316711D9F45E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Control of GnRH neuronal activity by metabolic factors: the role of leptin and insulin
Journal
Molecular and Cellular Endocrinology
Author(s)
Gamba  M., Pralong  F. P.
ISSN
0303-7207 (Print)
Publication state
Published
Issued date
07/2006
Volume
254-255
Pages
133-9
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Jul 25
Abstract
Energy balance exerts a critical influence on reproductive function. Leptin and insulin are among the metabolic factors signaling the nutritional status of an individual to the hypothalamus, and their role in the overall modulation of the activity of GnRH neurons is increasingly recognized. The experiments described here were designed to further investigate the central mechanisms of action of these two hormones and the precise hypothalamic pathways implicated in their effects on the reproductive axis. NPY neurons represent a primary target of leptin actions within the hypothalamus We used mice lacking the NPY Y1 receptor (Y1-/- mice) to investigate the physiological importance of the hypothalamic NPY neuronal system and its downstream pathways involving Y1 in the reproductive effects of leptin. Results point to a crucial role for the NPY Y1 receptor in the control of the onset of puberty and the maintenance of reproductive functions by leptin. A striking finding of these experiments was the observation that juvenile Y1-/- mice submitted to food restriction can proceed through puberty like normally fed animals, demonstrating that the absence of Y1 impairs the perception of decreasing energy stores by the gonadotrope axis. Next, we used parallel in vivo and in vitro experiments to delineate the role of insulin in the stimulation and maintenance of the activity of the neuroendocrine reproductive axis. First, we observed that the increase in circulating insulin levels achieved during hyperinsulinemic clamp studies in normal male mice was associated with a significant rise in LH secretion. This effect of insulin is likely mediated at the hypothalamic level, as insulin stimulates the secretion and the expression of GnRH by hypothalamic neurons in culture. Using primary neuronal cultures as well as a novel GnRH neuronal cell line obtained by conditional immortalization of adult rat hypothalamic neurons, we have recently demonstrated that this effect of insulin on GnRH gene expression is probably mediated directly at the level of GnRH neurons, and involves the stimulation of the MAP kinase Erk1/2 pathway. Taken together, these results provide new insights into the mechanisms involved in the regulation of GnRH neuronal activity by metabolic factors.
Keywords
Animals Gonadotropin-Releasing Hormone/*metabolism Humans Insulin/*physiology Leptin/*physiology Models, Biological Neurons/*metabolism Neuropeptide Y/physiology
Pubmed
Web of science
Create date
25/01/2008 16:26
Last modification date
20/08/2019 13:16
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