Growth factor expression in early stages of benign prostatic hyperplasia upon exposure to sustained delivery of androgens.

Benign prostatic hyperplasia (BPH) is a condition that affects a significant population of older males, yet its pathogenesis is not clearly understood. This study was designed to give broader insight into the early development of BPH by looking at changes in growth factor production in the ventral prostate. To accomplish this, Sprague Dawley rats (n = 16, 250-300 g) were randomly divided into four equal groups. Three treatment groups were each implanted with ceramic drug delivery devices that were designed to deliver continuous physiologic doses of testosterone (T), dihydrotestosterone (DHT), and androstenedione (AED) for ninety-day duration. Immuno-histochemical analysis for epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) indicated whether these growth factors were involved in early processes of BPH induced by the delivery of androgens. Histopathological evaluation demonstrated increased positive reactivity for both EGF and bFGF in all steroid treated animals compared to controls. A similar trend was observed in the vascular endothelium. This information could be helpful in developing new methods for early diagnosis of BPH, but more importantly this knowledge provides the literature with clues about the cellular responses encountered at the initiation of the disease process.

Cytopathological changes in early stages of benign prostatic hyperplasia upon exposure to sustained delivery of androgens.

The objective of this study was to assess the possible morphological changes that occur in the columnar epithelial cells of the prostate peripheral zone during early development of benign prostatic hyperplasia. In this study benign prostatic hyperplasia (BPH) was encouraged by the continuous delivery of androgens using TCPL drug delivery devices. A total of 16 adult male rats were randomly divided into four groups (n = 4). Group 1 served as an intact control and Groups 2-4 were implanted with tricalcium phosphate lysine (TCPL) capsules designed to deliver continuous physiologic (40 mg) doses of specific androgens as follows: Group 2, testosterone (Test); Group 3, dihydrotestosterone (DHT); Group 4, androstenedione (AED), respectively. Upon completion of the study, the columnar epithelial cells were targeted for morphometric analysis. The means number of cells per high power field, cell length, cell area, nuclear area and nuclear to cytoplasmic ratio were measured using image analysis techniques. The results of this study showed that (1) the number of cells per high power field were not changed with treatment, (2) the cell length was decreased with treatment of all androgens, (3) the cell area was decreased with treatment, (4) the nuclear area was increased with treatment of Test and DHT, and (5) the N/C ratio was increased with all three androgens. These results suggest that very early in the development of BPH, remarkable changes occur in the nucleus of the columnar epithelial cells. These changes may indicate a specific physiological response to irritation arising from the continuous delivery of androgens.