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.

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Citation

Volker P, Grundker C, Schmidt O, Schulz KD, Emons G

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.

Am J Obstet Gynecol. 2002 Feb;186(2):171-9.

PubMed ID
11854630 [ View in PubMed
]
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. 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. 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. 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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CetrorelixGonadotropin-releasing hormone receptorProteinHumans
Yes
Antagonist
Details