Document Detail

Follicular fluid high-density lipoprotein-associated sphingosine 1-phosphate (S1P) promotes human granulosa lutein cell migration via S1P receptor type 3 and small G-protein RAC1.
MedLine Citation:
PMID:  20980685     Owner:  NLM     Status:  MEDLINE    
Coordinated migration and progesterone production by granulosa cells is critical to the development of the corpus luteum, but the underlying mechanisms remain obscure. Sphingosine 1-phosphate (S1P), which is associated with follicular fluid high-density lipoprotein (FF-HDL), was previously shown to regulate ovarian angiogenesis. We herein examined the effects of S1P and FF-HDL on the function of granulosa lutein cells. Both FF-HDL and S1P induced migration of primary human granulosa lutein cells (hGCs) and the granulosa lutein cell line HGL5. In addition, FF-HDL but not S1P promoted progesterone synthesis, and neither of the two compounds stimulated proliferation of granulosa lutein cells. Polymerase chain reaction and Western blot experiments demonstrated the expression of S1P receptor type 1 (S1PR1), S1PR2, S1PR3, and S1PR5 but not S1PR4 in hGCs and HGL5 cells. The FF-HDL- and S1P-induced granulosa lutein cell migration was emulated by FTY720, an agonist of S1PR1, S1PR3, S1PR4, and S1PR5, and by VPC24191, an agonist of S1PR1 and S1PR3, but not by SEW2871 and phytosphingosine 1-phosphate, agonists of S1PR1 and S1PR4, respectively. In addition, blockade of S1PR3 with CAY1044, suramine, or pertussis toxin inhibited hGC and HGL5 cell migration toward FF-HDL or S1P, while blockade of S1PR1 and S1PR2 with W146 and JTE013, respectively, had no effect. Both FF-HDL and S1P triggered activation of small G-protein RAC1 and actin polymerization in granulosa cells, and RAC1 inhibition with Clostridium difficile toxin B or NSC23766 abolished FF-HDL- and S1P-induced migration. The FF-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum.
Steffi Becker; Soren von Otte; Horst Robenek; Klaus Diedrich; Jerzy-Roch Nofer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  Biology of reproduction     Volume:  84     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-23     Completed Date:  2011-06-14     Revised Date:  2013-02-05    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  604-12     Citation Subset:  IM    
Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
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MeSH Terms
Cell Movement* / drug effects,  genetics,  physiology
Cell Proliferation / drug effects
Cells, Cultured
Corpus Luteum / cytology,  drug effects,  metabolism
Follicular Fluid / chemistry,  metabolism*
Lipoproteins, HDL / analysis,  metabolism,  pharmacology
Luteal Cells / drug effects,  metabolism,  physiology*
Lysophospholipids / metabolism,  pharmacology,  physiology*
Monomeric GTP-Binding Proteins / metabolism,  physiology
Progesterone / analysis,  metabolism
Receptors, Lysosphingolipid / genetics,  metabolism,  physiology*
Sphingosine / analogs & derivatives*,  metabolism,  pharmacology,  physiology
rac1 GTP-Binding Protein / metabolism,  physiology*
Reg. No./Substance:
0/Lipoproteins, HDL; 0/Lysophospholipids; 0/RAC1 protein, human; 0/Receptors, Lysosphingolipid; 0/sphingosine-1-phosphate receptor-3, human; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 57-83-0/Progesterone; EC GTP-Binding Proteins; EC GTP-Binding Protein

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