Gonadotropin releasing hormone (GnRH)analog,([D-TrpE6]-luteinizing hormone-releasing hormone, [D-TrpE6]-LH-RH), can cause regression of hormone-dependent human tumors. These effects are thought to be mediated through inhibition of the
gonadotropic
and
steroid hormone.
But, it has been reported recnelty that this analog has a direct inhibitory effect on the tumor.
To evaluate the direct inhibitory effect of GnRH analog on ovarian tumors, the characteristics of membrane receptors for GnRH analog were investigated in tissues of normal human ovaries, human ovarian cancers obtained from srugery, and
heteroctransplanted nude mice tumors.
@ES The results were as follows;
@EN 1. In the heterotransplanted nude mice tumors, the inhibitory effect of GnRH analog on tumor growth was compared with untreated animals and in vivo treated animals with [D-TrpE6]-LH-RH. In the treated group showed significant growth
inhibition(p<0.001).
2. Specific binding of [125 I, D-TrpE6]-LH-RH were demonstrated in plasma membranes extracted from 7 human epithelial ovarian carcinomas and heterotransplanted nude mice tumors, but not in normal human ovaries.
3. In the plasma membrane preparations from ovarian cancer, statistical analysis of the binding data showed that the interaction of [D-TrpE6]-LH-RH with the binding sites was consistent with a single class of low affinity (Kd=2.1×10E-9)and high
capacity binding sites(Bmax=15.8±10.5×10E12M/mg membrane protein).
4. Therapy with [D-TrpE6]-LH-RH significantly decreased the binding capacity of receptors for [D-TrpE6]-LH-RH in heterotransplanted nude mice tumors(P<0.001).
5. We observed possible correlation between GnRH binding site density and the clinical corse of the patients, and found out that GnRH responded group showed a higher GnRH binding sites than that of non?responded group (P<0.05).
These findings are compatible with the view that [D-TrpE6]-LH-RH might exert some direct inhibitory effects on the growth of human ovarian and heterotransplanted nude mice ovarian tumors.
Although the functional role of this specific binding site for [D-TrpE6]-LH-RH in ovarian carcinoma is still obscure, it might be part of an autocrine regulatory system and provide that this malignancy might be responsive to hormonal
manipulations.
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