MORPHOLOGICAL AND HORMONAL CHANGES IN THE VENTRAL AND DORSOLATERAL PROSTATIC LOBES OF RATS TREATED WITH FINASTERIDE, A 5-ALPHA REDUCTASE INHIBITOR

BACKGROUND. In rats, the prostate is divided into three distinct lobes , and the lobes are dependent on androgens [testosterone (T) and dihyd rotestosterone (DHT)] as trophic hormones. However, the reasons for th e difference in the incidence of proliferative changes reported are no t well-understood. Administration of finasteride, a 5-alpha reductase (5 alpha R) inhibitor which selectively inhibits the conversion of T t o DHT, results in elevated intraprostatic T levels. However, long-term (2 years) administration of finasteride results in no increase in pro liferative changes in the ventral lobes of the rat prostate. Therefore , studies were designed to determine the differences in intraprostatic hormonal levels, morphology, and 5 alpha R activity in different lobe s of the rat prostate. METHODS. Sexually mature male Sprague-Dawley ra ts were used in all studies. Finasteride was administered orally to ra ts. The methodology included determination of intraprostatic T and DHT levels by radioimmunoassay, qualitative and quantitative evaluation o f prostatic morphology, and in vitro determination of 5 alpha R activi ties in rat prostatic lobes. RESULTS. A significant amount of 5 alpha R activity was observed in the dorsal, ventral, and lateral lobes of t he rat prostate. Both 5 alpha R isozymes (types 1 and 2) were present in all lobes, based on 5 alpha R activities observed at both acidic an d neutral pH. Oral administration of finasteride (160 mg/kg/day) for 1 5 days resulted in significant (P less than or equal to 0.001) decreas es in intraprostatic DHT levels and increases in T levels; when compar ed to controls, the mean decrease in DHT levels in the ventral and the dorsolateral lobes was 86% and 94%, respectively, and the mean increa se in T levels in the ventral and the dorsolateral lobes was approxima tely 3 times and 20 times, respectively, higher than in controls. Chro nic administration of finasteride (80 mg/kg/day) for 6 months resulted in significant (P less than or equal to 0.001) decreases in the weigh ts of the prostatic lobes, which correlated with significant (P less t han or equal to 0.001) decreases in the total number of epithelial and stromal cells per gland in both the ventral and dorsolateral lobes of the prostate. There were no qualitative differences in prostatic morp hology between the control and finasteride-treated groups. A short-ter m study in control rats ex posed to bromodeoxyuridine (Brdu) showed th at the number of Brdu-labeled cells in the dorsolateral lobe was signi ficantly (P less than or equal to 0.05) greater than in the ventral lo be. CONCLUSIONS. This first comparative study has highlighted some of the similarities and differences among the prostatic lobes of the rat. Inhibition of conversion of T to DHT with finasteride resulted in a s ignificant increase in intraprostatic T levels and a significant decre ase in DHT levels in rats; despite a significant increase in intrapros tatic T levels, the prostate remained atrophic, indicating that DHT al one has a trophic effect on the prostate. (C) 1998 Wiley-Liss, Inc.