PMID- 17003237
OWN - NLM
STAT- MEDLINE
DCOM- 20070319
LR  - 20181201
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 292
IP  - 2
DP  - 2007 Feb
TI  - 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.
PG  - E523-32
AB  - 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.
FAU - Chattopadhyay, Naibedya
AU  - Chattopadhyay N
AD  - 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
FAU - Jeong, Kyeong-Hoon
AU  - Jeong KH
FAU - Yano, Shozo
AU  - Yano S
FAU - Huang, Su
AU  - Huang S
FAU - Pang, Jian L
AU  - Pang JL
FAU - Ren, Xianghui
AU  - Ren X
FAU - Terwilliger, Ernest
AU  - Terwilliger E
FAU - Kaiser, Ursula B
AU  - Kaiser UB
FAU - Vassilev, Peter M
AU  - Vassilev PM
FAU - Pollak, Martin R
AU  - Pollak MR
FAU - Brown, Edward M
AU  - Brown EM
LA  - eng
GR  - AR-02115/AR/NIAMS NIH HHS/United States
GR  - DK-48330/DK/NIDDK NIH HHS/United States
GR  - DK-52005/DK/NIDDK NIH HHS/United States
GR  - DK-52479/DK/NIDDK NIH HHS/United States
GR  - DK-67111/DK/NIDDK NIH HHS/United States
GR  - DK-67155/DK/NIDDK NIH HHS/United States
GR  - HD-050412/HD/NICHD NIH HHS/United States
GR  - HD-19938/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060926
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, Chemokine)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/physiology
MH  - Cell Count
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - *Chemotaxis
MH  - Female
MH  - Gonadotropin-Releasing Hormone/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*cytology/*metabolism
MH  - Receptors, CCR2
MH  - Receptors, Calcium-Sensing/genetics/metabolism/*physiology
MH  - Receptors, Chemokine/metabolism
EDAT- 2006/09/28 09:00
MHDA- 2007/03/21 09:00
CRDT- 2006/09/28 09:00
PHST- 2006/09/28 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/09/28 09:00 [entrez]
AID - 00372.2005 [pii]
AID - 10.1152/ajpendo.00372.2005 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E523-32. doi: 
      10.1152/ajpendo.00372.2005. Epub 2006 Sep 26.