Evidence for coupling of phosphotyrosine phosphatase to gonadotropin-releasing hormone receptor in ovarian carcinoma membrane

Cancer. 1996 Jan 1;77(1):132-7. doi: 10.1002/(SICI)1097-0142(19960101)77:1<132::AID-CNCR22>3.0.CO;2-5.


Background: Gonadotropin-releasing hormone (Gn-RH) receptor (Gn-RHR) has been demonstrated in epithelial ovarian carcinoma (Imai et al., Cancer 1994; 74:2555-61). To examine whether Gn-RHR mediates direct antiproliferative effects, we attempted to determine stimulatory regulation by Gn-RH of phosphotyrosine phosphatase (PTP) activity in plasma membranes isolated from ovarian carcinoma samples.

Methods: Surgically removed ovarian carcinomas were screened for Gn-RHR expression prior to plasma membrane isolation. The phosphotyrosine level was observed by: (1) immunoblotting of membrane extracts with antiphosphotyrosine antibodies, and (2) dephosphorylation from 32P-labeled membrane protein. Membrane PTP activity was determined using the synthetic substrate p-nitrophenyl in a spectrophotometric assay.

Results: A Gn-RH analog alone, or guanosine thiotriphosphate (GTP-gamma-S) alone, caused a remarkable loss of phosphotyrosine from a 35-kD protein of the membranes; incubation with a Gn-RH analog and GTP-gamma-S produced a further dephosphorylation of this endogenous protein. The Gn-RH analog buserelin stimulated the PTP activity of the membranes in a dose-dependent manner (P < 0.01). GTP-gamma-S enhanced the stimulatory action of Gn-RH on PTP; GDP-gamma-S reversed the Gn-RH action. A similar stimulation of PTP was observed (P < 0.01) when carcinoma tissue slices were exposed to Gn-RH analog in vivo prior to assay in vitro.

Conclusions: Activation of PTP by Gn-RH stimulated the loss of phosphotyrosine from endogenous proteins through GTP-binding protein within plasma membrane isolated from Gn-RHR-expressing ovarian carcinoma. The antimitogenic action of the hormone may occur by counteracting tyrosine phosphorylation to promote cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / enzymology*
  • Female
  • GTP-Binding Proteins / metabolism
  • Gonadotropin-Releasing Hormone / metabolism*
  • Gonadotropin-Releasing Hormone / physiology*
  • Humans
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / ultrastructure
  • Protein Tyrosine Phosphatases / metabolism*
  • Tumor Cells, Cultured


  • Gonadotropin-Releasing Hormone
  • Protein Tyrosine Phosphatases
  • GTP-Binding Proteins