title: Signaling through FSH receptors on human umbilical vein endothelial cells promotes angiogenesis.
abstract: BACKGROUND
  The FSH receptor (FSHR) is traditionally thought to play a role in female reproductive physiology solely within the context of ovarian FSHR. However, FSHR is also expressed in endothelial cells of the placental vasculature and human umbilical cord vessels, suggesting additional facets of female reproduction regulated by extragonadal FSHR.
  
  
  OBJECTIVE
  We sought to determine the functional role of FSHR on human umbilical cord endothelial cells (HUVECs), hypothesizing that activation of the FSHR would stimulate angiogenesis.
  
  
  METHODS
  The ability of FSH to stimulate several angiogenic processes in HUVECs was determined.
  
  
  METHODS
  This was a laboratory-based study using commercially prepared HUVECs.
  
  
  RESULTS
  Tube formation, wound healing, cell migration, cell proliferation, nitric oxide production, and cell survival were stimulated in response to FSH. Quantitative comparisons between HUVECs incubated with maximally stimulatory concentrations of FSH vs vascular endothelial growth factor (VEGF), a well-characterized angiogenic factor, revealed that FSH is as efficacious as VEGF in promoting angiogenic processes. FSH did not provoke increased secretion of VEGF by HUVECs, suggesting the direct stimulation of angiogenic processes by FSH in endothelial cells. In contrast to gonadal cells, the FSHR on HUVECs did not mediate an FSH-stimulated increase in cAMP. However, increased phosphorylation of AKT in response to FSH was observed, suggesting that FSH stimulation of HUVEC FSHR stimulates the PI3K/AKT signaling pathway.
  
  
  CONCLUSIONS
  Our studies reveal a novel role for FSHR in female reproductive physiology. Its ability to promote angiogenesis in placental endothelial cells suggests that the FSHR may have an influential role in pregnancy.
authors: Department of Molecular Biophysics and Physiology (J.A.S., R.G., D.L.S.), The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242; and Department of Physiological Sciences (D.M.D.), Eastern Virginia Medical School, Norfolk, Virginia 23508.
authors: Julie A
authors: JA
authors: Stilley
authors: Rongbin
authors: R
authors: Guan
authors: Diane M
authors: DM
authors: Duffy
authors: Deborah L
authors: DL
authors: Segaloff
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D011962:Receptors, FSH; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt