FSH stimulates ovarian cancer cell growth by action on growth factor variant receptor

Mol Cell Endocrinol. 2007 Mar 15;267(1-2):26-37. doi: 10.1016/j.mce.2006.11.010. Epub 2007 Jan 16.


A number of FSH receptor (FSH-R) isoforms with distinct structural motifs and signaling paradigms have been described, including a single transmembrane domain variant that functions as a growth factor type receptor (FSH-R3). This study tested the hypothesis that FSH can stimulate ovarian cancer cell proliferation by acting on FSH-R3, using the tumorigenic mouse ovarian surface epithelial cell (MOSEC) line ID8. FSH enhanced ID8 proliferation in a concentration-dependent fashion. Moreover, FSH-treatment of ID8 elicited intracellular events consistent with activation of FSH-R3 and distinct from those associated with activation of the canonical G-protein coupled FSH-R isoform (FSH-R1). Specifically, the FSH-R3 signaling pathway included cAMP-independent activation of ERK downstream of an SNX-482 sensitive component likely to be the Cav2.3 calcium channel. Northern analysis using probes specific for exons 7 and 11 of FSH-R identified consistently only one 1.9kb transcript. Immunoblot analysis confirmed expression of FSH-R3 but not FSHR-1 in ID8. Together, these data suggest that FSH-R3 signaling promotes proliferation of ovarian cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing / drug effects
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclic AMP / metabolism
  • Enzyme Activation / drug effects
  • Exons / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutant Proteins / metabolism*
  • Ovarian Neoplasms / pathology*
  • Receptors, FSH / chemistry
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism*
  • Signal Transduction / drug effects
  • Swine
  • Transcription, Genetic / drug effects


  • Mutant Proteins
  • Receptors, FSH
  • Follicle Stimulating Hormone
  • Cyclic AMP
  • Extracellular Signal-Regulated MAP Kinases