Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines

Background: Ghrelin, a natural growth hormone secretagogue (GHS), has been identified in prostate carcinoma cell lines. Objectives: To investigate the presence of ghrelin and its receptors in human prostate tumours and in DU-145, PC-3 and LNCaP prostate carcinoma cell lines, and to assesss the effects of ghrelin and its more abundant circulating form, des-octanoyl ghrelin, on cell proliferation. Methods: Ghrelin and types la and 1b GHS receptor (GHS-R) were determined at the mRNA and protein levels by RT-PCR, in situ hybridization, immunohistochemistry and enzyme immunoassay in tissues, cell lines and culture medium. Ghrelin binding was determined by radioreceptor assay. The effects on cell proliferation were evaluated by growth curves. Results: Ghrelin mRNA was found in prostatic carcinomas and benign hyperplasias, but immunohistochemistry was negative. GHS-R1a and 1b mRNAs were absent from carcinomas, but GHS-R1b mRNA was present in 50% of hyperplasias. Ghrelin peptide and mRNA were present in PC-3 cells exclusively, whereas GHS-R1a and 1b mRNAs were expressed in DU-145 cells only. Specific [I-125]Tyr(4)-ghrelin binding was detected in prostate tumour, DU-145 and PC-3 cell membranes and the binding was displaced by ghrelin, synthetic GHS and des-octanoyl ghrelin, which is devoid of GHS-R1a binding affinity and GH-releasing activity. Ghrelin and des-acyl ghrelin inhibited DU-145 cell proliferation, displayed a biphasic effect in PC-3 cells and were ineffective in LNCaP cells. Conclusions: Specific GHS binding sites, other than GHS-R1a and 1b, are present in human prostatic neoplasms. Ghrelin, in addition to des-acyl ghrelin, exerts different effects on cell proliferation in prostate carcinoma cell lines.