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Urol Clin North Am. 1990 Aug;17(3):461-75.

Clinical and experimental studies of benign prostatic hyperplasia.

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  • 1James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland.

Abstract

The canine prostate appears to be a suitable model for investigating many aspects of abnormal prostate growth related to BPH. This model has indicated that BPH is a complex pathologic process that varies with age and produces a gland that is composed of a mixture of glandular, cystic, and stromal hyperplasia juxtapositioned with foci of atrophy. Canine BPH first occurs very early in life as a glandular hyperplasia before the onset of more complex BPH. As the prostate increases in size with age, the tissue dihydrotestosterone content falls, as does the secretory capacity of the gland. The fall in glandular dihydrotestosterone content is counterbalanced by a concomitant increase in the metabolism of androgens toward dihydrotestosterone and an increase in nuclear androgen receptors. As the prostate ages, it thus becomes more sensitive to androgens, which are required for maintaining the abnormal size of the gland. Established BPH can be maintained in the absence of the testes in the presence of normal testosterone levels, and it appears that the abnormal growth is primarily attributable to an inherent change that has occurred in the aged prostate. In the dog and man, both the normal prostate and BPH are rich in growth factors and dihydrotestosterone receptor in the nucleus, yet mitotic cells are rare. Established BPH is not growing rapidly; the abnormal size of the aged prostate is maintained, not by an increase in the rate of cell replication, but rather by an apparent decrease in the rate of cell death. It appears that a combination of estrogens and 5 alpha-reduced androgens can cause this decrease in the rate of cell death and replication and that this imbalance can produce abnormal cell accumulation and an experimental prostatic hyperplasia. Besides affecting cell death and replication, estradiol has a marked effect in stimulating the stroma and collagen synthesis. Current investigations are focusing on determining the distribution of stem cells for both the epithelial and the stromal elements of the prostate, how these stem cells are recruited to form transiently proliferating cells, and how they mature and subsequently are programmed for cell death. It is believed that steroid imprinting in the neonatal and prepubertal period may be of great importance in determining the ultimate growth of the prostate. Preliminary attempts to control abnormal canine prostate growth by forcing maturation with retinoic acid, or by interfering with growth factors through the use of suramin, have not proved effective; only androgen ablation is. Important leads in the search for the etiology and control of BPH can be studied in the canine model. These concepts must ultimately be tested and confirmed for human BPH in well-controlled clinical investigations.

PMID:
1695775
[PubMed - indexed for MEDLINE]
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