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Gonadotropin-releasing hormone stimulates phospholipase C but not protein phosphorylation/dephosphorylation in plasma membrane from human epithelial ovarian cancer*
  1. A. Imai,
  2. T. Ohno,
  3. T. Furui,
  4. K. Takahashi,
  5. T. Matsuda and
  6. T. Tamaya
  1. Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi, Gifu 500 Japan
  1. Address for correspondence: Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi, Gifu 500 Japan.

Abstract

In view of advances in treatment of certain hormone-dependent cancers with analogues of gonadotropin-releasing hormone (Gn-RH), this study was undertaken to establish the signal transduction events interacting with Gn-RH receptor in a cell-free system prepared from human ovarian mucinous cystadenocarcinoma samples. A high affinity specific binding (Kd=8 × 10−9 M) of [3H] Gn-RH was demonstrated in two from two plasma membrane preparations. Gn-RH showed no effects on the rate of protein phosphorylation from [γ-32P] adenosine triphosphate in the plasma membrane preparations. On the other hand, incubation of plasma membrane isolated form [3H]inositol-labeled specimens with Gn-RH in the presence of guanosine thiotriphosphate resulted in the rapid production of inositol phosphates. The Gn-RH effects was concentration-dependent, and half-maximal activation occurred with 1–3 nm Gn-RH. The Gn-RH-stimulated membrane event was observed in all plasma membrane isolations tested, but not in those from uterine endometrial carcinoma of a given case. These results provide the first direct evidence that Gn-RH receptor is coupled to phosphoinositide hydrolysis but not to certain membrane protein phosphorylation/dephosphorylation in ovarian carcinoma plasma membrane. Though the functional role of this event in human ovarian cancer is still obscure, it might be part of a possible point of attack for therapeutic approaches using Gn-RH analogues in this malignancy.

  • antitumor effect
  • gonadotropin-releasing hormone
  • ovarian cancer
  • phosphoinositide
  • receptor (human).

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Footnotes

  • *The work described in this paper was supported by research grants (#01570923, #04670996) from the Ministry of Education, Culture and Science, Japan.

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