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Endocrinology

Title:		Genetic identification of GnRH receptor neurons: a new model for studying neural circuits underlying reproductive physiology in the mouse brain
Author(s):		Wen S; Gotze IN; Mai O; Schauer C; Leinders-Zufall T; Boehm U;
Address:		"Institute for Neural Signal Transduction, Center for Molecular Neurobiology, Falkenried 94, D-20251 Hamburg, Germany"
Journal Title:		Endocrinology
Year:		2011
Volume:		20110208
Issue:		4
Page Number:		1515 - 1526
DOI:		10.1210/en.2010-1208
ISSN/ISBN:		1945-7170 (Electronic) 0013-7227 (Linking)
Abstract:		"GnRH signaling regulates reproductive physiology in vertebrates via the hypothalamic-pituitary-gonadal axis. In addition, GnRH signaling has been postulated to act on the brain. However, elucidating its functional role in the central nervous system has been hampered because of the difficulty in identifying direct GnRH signaling targets in live brain tissue. Here we used a binary genetic strategy to visualize GnRH receptor (GnRHR) neurons in the mouse brain and started to characterize these cells. First, we expressed different fluorescent proteins in GnRHR neurons and mapped their precise distribution throughout the brain. Remarkably, neuronal GnRHR expression was only initiated after postnatal day 16, suggesting peri- and postpubertal functions of GnRH signaling in this organ. GnRHR neurons were found in different brain areas. Many GnRHR neurons were identified in areas influencing sexual behaviors. Furthermore, GnRHR neurons were detected in brain areas that process olfactory and pheromonal cues, revealing one efferent pathway by which the neuroendocrine hypothalamus may influence the sensitivity towards chemosensory cues. Using confocal Ca(2+) imaging in brain slices, we show that GnRHR neurons respond reproducibly to extracellular application of GnRH or its analog [D-TRP(6)]-LH-RH, indicating that these neurons express functional GnRHR. Interestingly, the duration and shape of the Ca(2+) responses were similar within and different between brain areas, suggesting that GnRH signaling may differentially influence brain functions to affect reproductive success. Our new mouse model sets the stage to analyze the next level of GnRH signaling in reproductive physiology and behavior"
Keywords:		"Animals Brain/*metabolism Female Fluorescent Antibody Technique Hypothalamus/cytology/metabolism In Vitro Techniques Male Mice Neural Conduction/genetics/physiology Neurons/*metabolism Odorants Pheromones/metabolism Proteins/genetics/metabolism RNA, Untra;"
Notes:		"MedlineWen, Shuping Gotze, Iris N Mai, Oliver Schauer, Christian Leinders-Zufall, Trese Boehm, Ulrich eng Research Support, Non-U.S. Gov't 2011/02/10 Endocrinology. 2011 Apr; 152(4):1515-26. doi: 10.1210/en.2010-1208. Epub 2011 Feb 8"