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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 1 206-213
Copyright © 1998 by The Endocrine Society

Original Studies

A Novel Coculture Model for Benign Prostatic Hyperplasia Expressing Both Isoforms of 5{alpha}-Reductase1

Colin W. Bayne, Frank Donnelly, Karen Chapman, Prasad Bollina, Colin Buck and Fouad K. Habib

University Departments of Surgery (C.W.B., F.K.H.), Pathology (F.D.), Medicine (K.C.), and Urology (P.B.), Western General Hospital, Edinburgh; and the Department of Urology, Glasgow Royal Infirmary (C.B.), Glasgow, Scotland

Address all correspondence and requests for reprints to: Dr. Fouad K. Habib, University Department of Surgery, Western General Hospital, Edinburgh, Scotland EH4 2XU. E-mail: fkh{at}srvo.med.ed.ac.uk

We have developed a coculture system for primary fibroblast and epithelial cells derived from benign prostatic hyperplasia (BPH) that retained many of the characteristics of the intact human prostate. In contrast to separately cultured prostate fibroblast and epithelial cells, cocultures of fibroblasts and epithelial cells maintained messenger ribonucleic acid expression and functional activity for both isoenzymes of 5{alpha}-reductase (type I and type II) as well as maintained expression of androgen receptors and prostate-specific antigen. Furthermore, levels of prostate-specific antigen secreted by cocultured epithelial cells were increased by treatment with androgens, mimicking the situation in the human gland. This contrasted with conventionally cultured fibroblasts or epithelial cells, which failed to express 5{alpha}-reductase type II and rapidly lost expression of androgen receptors and androgen sensitivity upon being placed into culture. Electron microscopy demonstrated intracellular structures indicative of the differentiated state of the cocultured cell types, including round nuclei, tonofibrils, and microvilli in epithelial cells and elongated nuclei; large amounts of Golgi and cilia; along with immature collagen fibers in fibroblasts. The present study demonstrates that the coculture model reflects more closely the in vivo system for human BPH and is thus a far more suitable model for investigating the molecular and cellular events that underlie BPH than current in vitro systems.




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