Notch Signaling Pathway Regulates Progesterone Secretion in Murine Luteal Cells

Reprod Sci. 2015 Oct;22(10):1243-51. doi: 10.1177/1933719115572480. Epub 2015 Feb 20.

Abstract

Notch signaling is an evolutionarily conserved pathway, which involves in various cell life activities. Other studies and our report showed that the Notch signaling plays very important role in follicle development in mammalian ovaries. In luteal cells, Notch ligand, delta-like ligand 4, is involved in normal luteal vasculature. In this study, murine luteal cells were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT). We found that L-658,458 and DAPT treatment decrease basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion. On the contrary, overexpression of intracellular domain of Notch3 increased basal and hCG-stimulated progesterone secretion. Further studies demonstrated that Notch signaling regulated the expression of steroidogenic acute regulatory protein and CYP11A, 2 key enzymes for progesterone synthesis. In conclusion, Notch signaling plays important role in regulating progesterone secretion in murine luteal cells.

Keywords: Notch3; luteal cell; progesterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism
  • Chorionic Gonadotropin / pharmacology
  • Dipeptides / pharmacology
  • Female
  • Gene Expression Regulation, Enzymologic
  • Luteal Cells / drug effects*
  • Luteal Cells / metabolism*
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Progesterone / metabolism*
  • Receptor, Notch3
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction* / drug effects
  • Transfection

Substances

  • Chorionic Gonadotropin
  • Dipeptides
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • Notch3 protein, mouse
  • Phosphoproteins
  • Receptor, Notch3
  • Receptors, Notch
  • steroidogenic acute regulatory protein
  • Progesterone
  • Cholesterol Side-Chain Cleavage Enzyme