High affinity binding and direct antiproliferative effects of luteinizing hormone-releasing hormone analogs in human endometrial cancer cell lines

Günter Emons, Britta Schröder, Olaf Ortmann, Silke Westphalen, Klaus Dieter Schulz, Andrew V Schally

Research output: Contribution to journalArticle

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Abstract

Although specific binding sites for LH-releasing hormone (LHRH) and its analogs have been demonstrated in biopsy samples of human endometrial cancer, their biological significance remains obscure. In this study we evaluated whether binding sites for LHRH are also present in the human endometrial cancer cell lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/ low capacity binding site was detected in both lines: HEC-1A line, dissociation constant (Kd)1 = 5.7 × 10-9 mol/L, binding capacity (Bmax)1 = 78 fmol/106 cells; Ishikawa line, Kd1 = 4.2 × 10-9 mol/L, Bmax1 = 29 fmol/106 cells. In addition, a second class of low affinity/high capacity binding sites for LHRH was demonstrated (HEC-1A line, Kd2 = 1.4 × 10-6 mol/L, Bmax2 = 21 pmol/106 cells; Ishikawa, Kd2 = 4 × 10-6 mol/ L, Bmax2 = 32 pmol/106 cells). In the presence of 10-5 mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A and Ishikawa cell lines was significantly reduced to 76 ± 2% and 88 ± 4% of controls, respectively, after 24 h and to 64 ± 2% and 62 ± 2%, respectively, after 6 days. Dose-response experiments showed that lower concentrations (10-9 mol/L) of the agonist decreased the proliferation to 80 ± 1% for the HEC-1A line and 71 ± 2% of controls for the Ishikawa line after 6 days. Antiproliferative effects are enhanced by increasing the doses of triptorelin and were maximal in this series of experiments at 10-5 mol/ L, the proliferation in the HEC-1A line being 62 ± 1% and in the Ishikawa line 52 ± 2% of controls, respectively. Similar time- and dose-dependent antiproliferative effects were obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These data suggest that LHRH analogs can directly inhibit the proliferation of human endometrial cancer cells in vitro. This direct action could be mediated through the high affinity LHRH binding sites.

Original languageEnglish
Pages (from-to)1458-1464
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume77
Issue number6
StatePublished - Dec 1 1993
Externally publishedYes

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Endometrial Neoplasms
Gonadotropin-Releasing Hormone
Cells
Cell Line
Binding Sites
Triptorelin Pamoate
Hormone Antagonists
Biopsy
Experiments
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

High affinity binding and direct antiproliferative effects of luteinizing hormone-releasing hormone analogs in human endometrial cancer cell lines. / Emons, Günter; Schröder, Britta; Ortmann, Olaf; Westphalen, Silke; Schulz, Klaus Dieter; Schally, Andrew V.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 77, No. 6, 01.12.1993, p. 1458-1464.

Research output: Contribution to journalArticle

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abstract = "Although specific binding sites for LH-releasing hormone (LHRH) and its analogs have been demonstrated in biopsy samples of human endometrial cancer, their biological significance remains obscure. In this study we evaluated whether binding sites for LHRH are also present in the human endometrial cancer cell lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/ low capacity binding site was detected in both lines: HEC-1A line, dissociation constant (Kd)1 = 5.7 × 10-9 mol/L, binding capacity (Bmax)1 = 78 fmol/106 cells; Ishikawa line, Kd1 = 4.2 × 10-9 mol/L, Bmax1 = 29 fmol/106 cells. In addition, a second class of low affinity/high capacity binding sites for LHRH was demonstrated (HEC-1A line, Kd2 = 1.4 × 10-6 mol/L, Bmax2 = 21 pmol/106 cells; Ishikawa, Kd2 = 4 × 10-6 mol/ L, Bmax2 = 32 pmol/106 cells). In the presence of 10-5 mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A and Ishikawa cell lines was significantly reduced to 76 ± 2{\%} and 88 ± 4{\%} of controls, respectively, after 24 h and to 64 ± 2{\%} and 62 ± 2{\%}, respectively, after 6 days. Dose-response experiments showed that lower concentrations (10-9 mol/L) of the agonist decreased the proliferation to 80 ± 1{\%} for the HEC-1A line and 71 ± 2{\%} of controls for the Ishikawa line after 6 days. Antiproliferative effects are enhanced by increasing the doses of triptorelin and were maximal in this series of experiments at 10-5 mol/ L, the proliferation in the HEC-1A line being 62 ± 1{\%} and in the Ishikawa line 52 ± 2{\%} of controls, respectively. Similar time- and dose-dependent antiproliferative effects were obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These data suggest that LHRH analogs can directly inhibit the proliferation of human endometrial cancer cells in vitro. This direct action could be mediated through the high affinity LHRH binding sites.",
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T1 - High affinity binding and direct antiproliferative effects of luteinizing hormone-releasing hormone analogs in human endometrial cancer cell lines

AU - Emons, Günter

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AU - Westphalen, Silke

AU - Schulz, Klaus Dieter

AU - Schally, Andrew V

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N2 - Although specific binding sites for LH-releasing hormone (LHRH) and its analogs have been demonstrated in biopsy samples of human endometrial cancer, their biological significance remains obscure. In this study we evaluated whether binding sites for LHRH are also present in the human endometrial cancer cell lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/ low capacity binding site was detected in both lines: HEC-1A line, dissociation constant (Kd)1 = 5.7 × 10-9 mol/L, binding capacity (Bmax)1 = 78 fmol/106 cells; Ishikawa line, Kd1 = 4.2 × 10-9 mol/L, Bmax1 = 29 fmol/106 cells. In addition, a second class of low affinity/high capacity binding sites for LHRH was demonstrated (HEC-1A line, Kd2 = 1.4 × 10-6 mol/L, Bmax2 = 21 pmol/106 cells; Ishikawa, Kd2 = 4 × 10-6 mol/ L, Bmax2 = 32 pmol/106 cells). In the presence of 10-5 mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A and Ishikawa cell lines was significantly reduced to 76 ± 2% and 88 ± 4% of controls, respectively, after 24 h and to 64 ± 2% and 62 ± 2%, respectively, after 6 days. Dose-response experiments showed that lower concentrations (10-9 mol/L) of the agonist decreased the proliferation to 80 ± 1% for the HEC-1A line and 71 ± 2% of controls for the Ishikawa line after 6 days. Antiproliferative effects are enhanced by increasing the doses of triptorelin and were maximal in this series of experiments at 10-5 mol/ L, the proliferation in the HEC-1A line being 62 ± 1% and in the Ishikawa line 52 ± 2% of controls, respectively. Similar time- and dose-dependent antiproliferative effects were obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These data suggest that LHRH analogs can directly inhibit the proliferation of human endometrial cancer cells in vitro. This direct action could be mediated through the high affinity LHRH binding sites.

AB - Although specific binding sites for LH-releasing hormone (LHRH) and its analogs have been demonstrated in biopsy samples of human endometrial cancer, their biological significance remains obscure. In this study we evaluated whether binding sites for LHRH are also present in the human endometrial cancer cell lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/ low capacity binding site was detected in both lines: HEC-1A line, dissociation constant (Kd)1 = 5.7 × 10-9 mol/L, binding capacity (Bmax)1 = 78 fmol/106 cells; Ishikawa line, Kd1 = 4.2 × 10-9 mol/L, Bmax1 = 29 fmol/106 cells. In addition, a second class of low affinity/high capacity binding sites for LHRH was demonstrated (HEC-1A line, Kd2 = 1.4 × 10-6 mol/L, Bmax2 = 21 pmol/106 cells; Ishikawa, Kd2 = 4 × 10-6 mol/ L, Bmax2 = 32 pmol/106 cells). In the presence of 10-5 mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A and Ishikawa cell lines was significantly reduced to 76 ± 2% and 88 ± 4% of controls, respectively, after 24 h and to 64 ± 2% and 62 ± 2%, respectively, after 6 days. Dose-response experiments showed that lower concentrations (10-9 mol/L) of the agonist decreased the proliferation to 80 ± 1% for the HEC-1A line and 71 ± 2% of controls for the Ishikawa line after 6 days. Antiproliferative effects are enhanced by increasing the doses of triptorelin and were maximal in this series of experiments at 10-5 mol/ L, the proliferation in the HEC-1A line being 62 ± 1% and in the Ishikawa line 52 ± 2% of controls, respectively. Similar time- and dose-dependent antiproliferative effects were obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These data suggest that LHRH analogs can directly inhibit the proliferation of human endometrial cancer cells in vitro. This direct action could be mediated through the high affinity LHRH binding sites.

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