rdf:type |
|
lifeskim:mentions |
umls-concept:C0008018,
umls-concept:C0023610,
umls-concept:C0026809,
umls-concept:C0027882,
umls-concept:C0032659,
umls-concept:C0035647,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0249742,
umls-concept:C0392756,
umls-concept:C1337092,
umls-concept:C1522558,
umls-concept:C1533691,
umls-concept:C1705079
|
pubmed:issue |
2
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pubmed:dateCreated |
2007-2-6
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pubmed:abstractText |
The factors controlling the migration of mammalian gonadotropin-releasing hormone (GnRH) neurons from the nasal placode to the hypothalamus are not well understood. We studied whether the extracellular calcium-sensing receptor (CaR) promotes migration/chemotaxis of GnRH neurons. We demonstrated expression of CaR in GnRH neurons in the murine basal forebrain and in two GnRH neuronal cell lines: GT1-7 (hypothalamus derived) and GN11 (olfactory bulb derived). Elevated extracellular Ca(2+) concentrations promoted chemotaxis of both cell types, with a greater effect in GN11 cells. This effect was CaR mediated, as, in both cell types, overexpression of a dominant-negative CaR attenuated high Ca(2+)-stimulated chemotaxis. We also demonstrated expression of a beta-chemokine, monocyte chemoattractant protein-1 (MCP-1), and its receptor, CC motif receptor-2 (CCR2), in the hypothalamic GnRH neurons as well as in GT1-7 and GN11 cells. Exogenous MCP-1 stimulated chemotaxis of both cell lines in a dose-dependent fashion; the effect was greater in GN11 than in GT1-7 cells, consistent with the higher CCR2 mRNA levels in GN11 cells. Activating the CaR stimulated MCP-1 secretion in GT1-7 but not in GN11 cells. MCP-1 secreted in response to CaR stimulation is biologically active, as conditioned medium from GT1-7 cells treated with high Ca(2+) promoted chemotaxis of GN11 cells, and this effect was partially attenuated by a neutralizing antibody to MCP-1. Finally, in the preoptic area of anterior hypothalamus, the number of GnRH neurons was approximately 27% lower in CaR-null mice than in mice expressing the CaR gene. We conclude that the CaR may be a novel regulator of GnRH neuronal migration likely involving, in part, MCP-1.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Gonadotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcium-Sensing,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
|
pubmed:issn |
0193-1849
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pubmed:author |
pubmed-author:BrownEdward MEM,
pubmed-author:ChattopadhyayNaibedyaN,
pubmed-author:HuangSuS,
pubmed-author:JeongKyeong-HoonKH,
pubmed-author:KaiserUrsula BUB,
pubmed-author:PangJian LJL,
pubmed-author:PollakMartin RMR,
pubmed-author:RenXianghuiX,
pubmed-author:TerwilligerErnestE,
pubmed-author:VassilevPeter MPM,
pubmed-author:YanoShozoS
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pubmed:issnType |
Print
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pubmed:volume |
292
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
E523-32
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17003237-Animals,
pubmed-meshheading:17003237-Calcium,
pubmed-meshheading:17003237-Cell Count,
pubmed-meshheading:17003237-Cells, Cultured,
pubmed-meshheading:17003237-Chemokine CCL2,
pubmed-meshheading:17003237-Chemotaxis,
pubmed-meshheading:17003237-Female,
pubmed-meshheading:17003237-Gonadotropin-Releasing Hormone,
pubmed-meshheading:17003237-Mice,
pubmed-meshheading:17003237-Mice, Knockout,
pubmed-meshheading:17003237-Neurons,
pubmed-meshheading:17003237-Receptors, CCR2,
pubmed-meshheading:17003237-Receptors, Calcium-Sensing,
pubmed-meshheading:17003237-Receptors, Chemokine
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pubmed:year |
2007
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pubmed:articleTitle |
Calcium receptor stimulates chemotaxis and secretion of MCP-1 in GnRH neurons in vitro: potential impact on reduced GnRH neuron population in CaR-null mice.
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pubmed:affiliation |
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine and Membrane Biology Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Naibedya@cdriindia.org
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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