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Expression of the Messenger RNAs for Luteinizing Hormone-releasing Hormone (LHRH) and Its Receptor in Human Ovarian Epithelial Carcinoma¹

Department of Obstetrics and Gynecology [G. I., O. O., U. P., K-D. S., G. E.] and Institute for Molecular Biology and Tumor Research [C. B., R. M.], Philipps University, D-35033 Marburg, Germany, and Department of Physiology and Biophysics [S. S. K., J. D. N.], University of Alabama at Birmingham, Birmingham, Alabama 35294

Recently we reported the presence of specific high affinity binding sites for luteinizing hormone-releasing hormone (LHRH) and its analogues (K_d = 1.5 or 1.7 nM) in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27. The proliferation of these cell lines was inhibited by nM concentrations of a LHRH agonist. This study was performed to ascertain whether these ovarian cancer cell lines produce LHRH and whether the high affinity LHRH binding site found previously was identical to the pituitary LHRH receptor. Significant amounts of immunoreactive LHRH were found in the extracts of both the EFO-21 cell line (449 ± 56 fmol/10⁶ cells) and the EFO-27 line (409 ± 76 fmol/10⁶ cells). LHRH bioactivity of these extracts, assessed in terms of release of luteinizing hormone by rat pituitary cells, was comparable to that of authentic LHRH. EFO-21 and EFO-27 cells expressed the mRNAs for both human LHRH and human LHRH receptor as assessed by reverse transcriptase-PCR using oligonucleotide primers according to published sequences. In addition, in eight of eight biopsy samples of human epithelial ovarian cancers we detected mRNA for LHRH, six of these specimens expressed the mRNA representing the LHRH receptor. These data support the concept that human epithelial ovarian cancers might have a local system based on LHRH to regulate cell proliferation. It is still obscure at present whether LHRH produced locally has a stimulatory, inhibitory, or no impact on the proliferation of ovarian cancer cells. However, exogenous LHRH agonists seem to have clear antiproliferative activity, probably mediated through LHRH receptors. This finding might provide the base for novel approaches in the therapy of epithelial ovarian cancer.

¹ This study was supported by the Deutsche Forschungsgemeinschaft (SFB 215, B10) and Graduiertenkolleg "Zell- und Tumorbiologie" (Marburg, Germany), P. E. Kempkes Foundation (Marburg, Germany), and Ferring Arzneimittel (Kiel, Germany), and by NIH Grant CA 60871.

² To whom requests for reprints should be addressed, at Department of Obstetrics and Gynecology, Philipps-University, Pilgrimstein 3, D-35033 Marburg, Germany.

Received 6/28/94. Accepted 12/ 7/94.

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