GENE-EXPRESSION AND AUTORADIOGRAPHIC LOCALIZATION OF ENDOTHELIN-1 ANDITS RECEPTOR-A AND RECEPTOR-B IN THE DIFFERENT ZONES OF THE NORMAL HUMAN PROSTATE

Purpose: To investigate the gene expression and tissue distribution of prepro Endothelin-1 (ET-1), Endothelin Converting Enzyme (hECE-1), an d ETA and ETB receptors in the central (CZ), transition (TZ) and perip heral (PZ) zones of normal human prostates. Materials and Methods: Sec tions of the different zones of histologically normal prostates from 3 5 year-old men were obtained and autoradiographically studied with I-1 25 ET-1 With and without the ETA antagonist BQ-123, the ETB agonists s arafotoxin 6C, and excess cold ET-1. Specimens from PZ and CZ and DU14 5 and PC3 human prostate cancer cell lines were also investigated by r everse transcription (RT)-PCR. Results: The mRNAs of all genes were de tected in all specimens examined. No ETB expression was found in eithe r cell lines. Specific intense I-125 ET-1 binding with clear-cut diffe rences among zones was found. In the CZ the main subtype in the glandu lar stroma and epithelium was the ETA and ETB, respectively, in the PZ the opposite was true. In PZ, the ETA receptors were detected on the glandular epithelium; in the TZ both receptor subtypes were only in th e stroma.Conclusions: These receptors' zonal distribution differences may be relevant for the pathogenesis of BPH and prostatic cancer.