Expression of chemokine CXCL12 and its receptor CXCR4 in folliculostellate (FS) cells of the rat anterior pituitary gland: the CXCL12/CXCR4 axis induces interconnection of FS cells

Endocrinology. 2012 Apr;153(4):1717-24. doi: 10.1210/en.2011-1937. Epub 2012 Feb 21.

Abstract

The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines
  • Cell Communication / drug effects
  • Cell Communication / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Surface Extensions / drug effects
  • Cell Surface Extensions / physiology
  • Cells, Cultured
  • Chalcone / pharmacology
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / drug effects
  • Chemokine CXCL12 / metabolism*
  • Cyclams
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heterocyclic Compounds / pharmacology
  • In Vitro Techniques
  • Male
  • Models, Animal
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Pituitary Gland, Anterior / cytology*
  • Pituitary Gland, Anterior / drug effects
  • Pituitary Gland, Anterior / metabolism*
  • Rats
  • Rats, Transgenic
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / drug effects
  • Receptors, CXCR4 / metabolism*
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / genetics
  • S100 Proteins / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Benzylamines
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Cyclams
  • Heterocyclic Compounds
  • Nerve Growth Factors
  • Receptors, CXCR4
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • Green Fluorescent Proteins
  • Chalcone
  • plerixafor