The major hypotheses to be examined by these studies are: 1) that chronic leukocyte infiltration into the prostate gland is a significant factor in the pathogenesis of human benign prostatic hyperplasia (BPH) and 2) that this leukocyte infiltration can be hormonally-mediated. The animal model to be used is the rat lateral prostate. The principal investigator has confirmed and extended earlier observations that the lateral prostate of the Wistar rat is the site of an infiltration by leukocytes that is both age-related and lobe-specific. The patterns of inflammation and the subsequent proliferation of fibromuscular tissue are strikingly similar to that observed in human BPH. Since human BPH primarily involves the fibromuscular stroma, the rat lateral prostate is believed to be histologically more relevant to the human problem than the dog model where hyperplasia is confined primarily to the epithelium. The overall approach will be to induce fibromuscular hyperplasia secondary to hormone-stimulated leukocyte infiltration into the lateral prostate of the castrated Wistar rat. Dose-response curves will be developed for the infiltration of leukocytes into the lateral prostate during the subacute administration of dihydrotestosterone (DHT) and/or estradiol. The number of leukocytes present will be determined by the development of appropriate flow cytometry techniques. Hypophysectomized animals or a prolactin release blocker (2-bromoergocryptine) will be used in selected cases to segregate the direct prostatic effects of the steroids from those mediated indirectly by hypothalamic factors or by estradiol-stimulated prolactin release, respectively. Using the conditions determined to be optimal for white cell infiltration on a subacute basis, chronic studies will be initiated in an attempt to induce fibromuscular hyperplasia secondary to hormone-stimulated leukocyte infiltration. Parallel chronic studies using inhibitors of prostatic leukocyte migration will be employed to segregate the direct effects of the hormone(s) on the prostate from the indirect effects mediated by white cells. Results obtained under these experimental conditions will be correlated with spontaneous rat hyperplasia occurring during the aging process.
| Tangbanluekal, L; Robinette, C L (1993) Prolactin mediates estradiol-induced inflammation in the lateral prostate of Wistar rats. Endocrinology 132:2407-16 |
| Robinette, C L (1988) Sex-hormone-induced inflammation and fibromuscular proliferation in the rat lateral prostate. Prostate 12:271-86 |
