In view of advancements in treatment of certain hormone-dependent cancers with analogues of luteinizing hormone-releasing hormone (LH-RH), this study was undertaken to establish the presence and characteristics of receptors for [d-Trp6]LH-RH on the membranes of human endometrial cancer. Specific binding of [125I,d-Trp6]LH-RH was demonstrated in membrane preparations from 24 of 31 (77%) endometrial carcinomas and from 3 of 13 (23.1%) nonmalignant human endometrial specimens. Ligand binding was dependent on temperature, time, and plasma membrane concentration in a fashion expected of a peptide hormone. Mathematical analysis of the binding data showed that interaction of [125I,d-Trp6]LH-RH with the binding sites was consistent with the presence of a single class of high affinity, noncooperative receptors (Kd 9.88 ± 4.59 × 10-9m; Bmax 0.70 ± 0.14 × 10-12 mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 × 106m-1 min-1 and 0.021 min-1, respectively. [125I,d-Trp6]LH-RH binding was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by native LH-RH. Using 125I-epidermal growth factor, specific, high-affinity receptors were also detected in membranes from 22 of 26 (85%) endometrial cancers and in all of 6 nonmalignant endometrial specimens (Kd 0.42 ± 0.12 × 10-9m; Bmax 0.30 ± 0.15 × 10-12 mol/mg membrane protein). The potential functional role of the receptors for [d-Trp6]LH-RH in human endometrial carcinoma is not clear, but this finding provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy.

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The work described in this paper was supported by NIH Grants CA 40004 (to A. V. S.), the Medical Research Service of the Veterans Administration, G. Harold and Leila Y. Mathers Foundation, United States Cancer Research Council (A. V. S.), and the Phi Beta Psi Sorority (J. L. W.).

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