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Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues.
- Source :
-
American journal of obstetrics and gynecology [Am J Obstet Gynecol] 2002 Feb; Vol. 186 (2), pp. 171-9. - Publication Year :
- 2002
-
Abstract
- Objective: Several recent reports have demonstrated the expression of luteinizing hormone-releasing hormone receptors by human ovarian and endometrial cancers. Controversy persists on the relevance of this finding, in particular whether these receptors mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. We correlated the expression of luteinizing hormone-releasing hormone receptors by well-characterized ovarian and endometrial cancer cell lines with the ability of luteinizing hormone-releasing hormone analogues to reduce their proliferation and studied the autoregulation of luteinizing hormone-releasing hormone receptor expression by luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix. The expression of luteinizing hormone-releasing hormone receptors was assessed in a series of specimens from primary ovarian and endometrial cancers.<br />Study Design: Luteinizing hormone-releasing hormone receptor expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction and radioligand binding assay. Antiproliferative effects were ascertained by proliferation assays in the absence or presence of luteinizing hormone-releasing hormone analogues.<br />Results: Ovarian (4/6 cell lines) and endometrial (5/6 cell lines) cancer cell lines expressed luteinizing hormone-releasing hormone receptors. The proliferation of these luteinizing hormone-releasing hormone receptor-positive cell lines was dose- and time-dependently reduced by agonistic and antagonistic luteinizing hormone-releasing hormone analogues. Luteinizing hormone-releasing hormone receptor density was reduced to 80% of controls (control, 100 %; P <.001) by luteinizing hormone-releasing hormone analogues. Seventy percent of primary ovarian cancers and 83% of primary endometrial cancers expressed luteinizing hormone-releasing hormone receptors.<br />Conclusion: These findings suggest that luteinizing hormone-releasing hormone receptors that are expressed by human ovarian and endometrial cancer cell lines mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. Because most respective primary cancers expressed luteinizing hormone-releasing hormone receptors, these receptors might be used for novel antiproliferative therapeutic approaches and should be further evaluated.
- Subjects :
- Binding Sites drug effects
Binding, Competitive
Cell Division drug effects
Female
Homeostasis
Humans
RNA, Messenger metabolism
Receptors, LHRH genetics
Triptorelin Pamoate metabolism
Triptorelin Pamoate pharmacology
Tumor Cells, Cultured
Endometrial Neoplasms metabolism
Ovarian Neoplasms metabolism
Receptors, LHRH metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9378
- Volume :
- 186
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of obstetrics and gynecology
- Publication Type :
- Academic Journal
- Accession number :
- 11854630
- Full Text :
- https://doi.org/10.1067/mob.2002.119633