title: Detection and partial characterization of receptors for [D-Trp6]-luteinizing hormone-releasing hormone and epidermal growth factor in human endometrial carcinoma.
abstract: 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 x 10(-9) M; Bmax 0.70 +/- 0.14 x 10(-12) mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 x 10(6) M-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 x 10(-9) M; Bmax 0.30 +/- 0.15 x 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.
authors.affiliation: Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana 70146.
authors.forename: G
authors.initials: G
authors.lastname: Srkalovic
authors.forename: J L
authors.initials: JL
authors.lastname: Wittliff
authors.forename: A V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D000230:Adenocarcinoma / Q000032:analysis* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002462:Cell Membrane / Q000032:analysis / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D011966:Receptors, LHRH / Q000032:analysis* / Q000378:metabolism; D017329:Triptorelin Pamoate; D014594:Uterine Neoplasms / Q000032:analysis* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D066246:ErbB Receptors