Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor.
BACKGROUND
The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time- and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently, we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was dose- and time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists.


OBJECTIVE
In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor.


METHODS
We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines.


RESULTS
We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted.


CONCLUSIONS
These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.
Gründker
Carsten
C
Department of Gynecology and Obstetrics, Georg-August-University, D-37070 Göttingen, Germany.
Schlotawa
Lars
L
Viereck
Volker
V
Eicke
Nicola
N
Horst
Anika
A
Kairies
Britta
B
Emons
Günter
G
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D016889:Endometrial Neoplasms; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D016296:Mutagenesis; D010051:Ovarian Neoplasms; D011966:Receptors, LHRH / Q000235:genetics; D017329:Triptorelin Pamoate / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; C484844:GNRHR protein, human; C427484:GNRHR2 protein, human; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-; C062876:cetrorelix