Detection and Partial Characterization of Receptors for [D-Trp6]-Luteinizing Hormone-releasing Hormone and Epidermal Growth Factor in Human Endometrial Carcinoma

Gordan Srkalovic, Andrew V. Schally, James L. Wittliff

Research output: Contribution to journalArticle

115 Scopus citations

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 × 10-9 M; Bmax 0.70 ± 0.14 × 10-12 mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 × 106 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 × 10-9 M; 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.

Original languageEnglish (US)
Pages (from-to)1841-1846
Number of pages6
JournalCancer Research
Volume50
Issue number6
StatePublished - Mar 15 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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