Gonadotropin releasing hormone binding sites in human epithelial ovarian carcinomata.
As a first step to investigate whether gonadotropin releasing hormone (GnRH) analogs might be able to modulate directly the proliferation of human epithelial ovarian carcinomata, we checked if binding sites for GnRH are present in these malignancies. Specific binding of [125I][D-Ala6-des Gly10]-GnRH-ethylamide (GnRH agonist = GnRH-A) could be demonstrated in plasma membranes from 32 out of 40 ovarian carcinomata tested. This binding was dependent on temperature, time and plasma membrane concentration. Mathematical analysis of the binding data showed that the interaction of GnRH-A with the binding sites was consistent with a single class of low affinity, high capacity binding sites (Ka = 1.42 +/- 0.14 X 10(5) M-1; range: 0.3-3.8 X 10(5) M-1; R = 209 +/- 69 X 10(-12) M/mg membrane protein; range 16-400 X 10(-12) M/mg MP; means +/- S.E., n = 32). Native GnRH and the GnRH antagonist [D-p-Glu1, D-Phe2, D-Trp3,6]-GnRH had Ka values comparable to those of the GnRH-A used. [125I]GnRH-A binding could not be displaced by oxytocin, thyrotropin releasing hormone and corticotropin releasing factor in concentrations up to 10(-4) M. Somatostatin cross-reacted with binding sites from some carcinomata, while it did not displace GnRH-A binding in membranes from others. Though the functional role of this specific binding site for GnRH in human epithelial ovarian carcinomata is still obscure, it might be part of an autocrine regulatory system and provide a possible point of attack for therapeutic approaches using GnRH analogs in this malignancy.
Emons
G
G
Department of Obstetrics and Gynecology, Medical University of Lübeck, F.R.G.
Pahwa
G S
GS
Brack
C
C
Sturm
R
R
Oberheuser
F
F
Knuppen
R
R
D000230:Adenocarcinoma / Q000378:metabolism; D001665:Binding Sites; D002291:Carcinoma, Papillary / Q000378:metabolism; D005260:Female; D006801:Humans; D008433:Mathematics; D008565:Membrane Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
D008565:Membrane Proteins; D010906:Pituitary Hormone-Releasing Hormones