Localization of Notch signaling molecules and their effect on cellular proliferation in adult rat pituitary

Cell Tissue Res. 2013 Mar;351(3):511-9. doi: 10.1007/s00441-012-1532-3. Epub 2012 Dec 12.

Abstract

Notch signaling is a cell-to-cell signaling system involved in the maintenance of precursor cells in many tissues. Although Notch signaling has been reported in the pituitary gland, the histological characteristics of Notch receptors and ligands in the gland are unknown. Here, we report the histological gene expression pattern of Notch receptors and ligands and the role of Notch signaling in cellular proliferation in adult rat pituitary gland. In situ hybridization detected transcripts of Notch1 and 2 and Jagged1 and 2. Double-staining with a combination of in situ hybridization and immunohistochemistry revealed that their mRNAs were localized in almost half of the S100-protein-positive cells, which are generally regarded as marginal layer cells and folliculo-stellate cells. In primary culture of anterior pituitary cells, proliferation of S100-protein-positive cells was modulated by Notch signaling inhibitor and solubilized Notch ligand. Furthermore, quantitative analysis revealed that the inhibition of Notch signaling led to the down-regulation of mRNA for the Notch target gene Hes1 and the up-regulation of p57 gene expression. These findings suggest that Notch signaling is involved in the proliferation of S100-protein-positive cells, presumably precursor cells, in adult rat pituitary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
  • Dipeptides / pharmacology
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Jagged-1 Protein
  • Ligands
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Pituitary Gland / cytology
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • Protein Transport / drug effects
  • RNA Transport / drug effects
  • RNA Transport / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • S100 Proteins / metabolism
  • Serrate-Jagged Proteins
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Solubility
  • Transcription Factor HES-1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Dipeptides
  • Hes1 protein, rat
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Jag1 protein, rat
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • RNA, Messenger
  • Receptors, Notch
  • S100 Proteins
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • Green Fluorescent Proteins