Hormonal regulation of pigment epithelium-derived factor (PEDF) in granulosa cells

Mol Hum Reprod. 2013 Feb;19(2):72-81. doi: 10.1093/molehr/gas046. Epub 2012 Oct 16.


Angiogenesis is critical for the development of ovarian follicles. Blood vessels are abrogated from the follicle until ovulation, when they invade it to support the developing corpus luteum. Granulosa cells are known to secrete anti-angiogenic factors that shield against premature vascularization; however, their molecular identity is yet to be defined. In this study we address the physiological role of pigment epithelium-derived factor (PEDF), a well-known angiogenic inhibitor, in granulosa cells. We have shown that human and mouse primary granulosa cells express and secrete PEDF, and characterized its hormonal regulation. Stimulation of granulosa cells with increasing doses of estrogen caused a gradual decrease in the PEDF secretion, while stimulation with progesterone caused an abrupt decrease in its secretion. Moreover, We have shown, by time- and dose-response experiments, that the secreted PEDF and vascular endothelial growth factor (VEGF) were inversely regulated by hCG; namely, PEDF level was nearly undetectable under high doses of hCG, while VEGF level was significantly elevated. The anti-angiogenic nature of the PEDF secreted from granulosa cells was examined by migration, proliferation and tube formation assays in cultures of human umbilical vein endothelial cells. Depleting PEDF from primary granulosa cells conditioned media accelerated endothelial cells proliferation, migration and tube formation. Collectively, the dynamic expression of PEDF that inversely portrays VEGF expression may imply its putative role as a physiological negative regulator of follicular angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Female
  • Granulosa Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mice
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Ovary / cytology
  • Ovary / metabolism
  • Serpins / genetics
  • Serpins / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor