The synergistic effect of sustained delivery of DHT, DHEA, and E on the ventral prostate of adult male rodents.

Previously, our laboratory has reported that tricalcium phosphate lysine drug delivery system (TCPL) can be used successfully to deliver dihydrotestosterone (DHT) and testosterone (T) at a sustained manner for long duration. The objective of this study was to evaluate the effects of estrogen (E), DHT and dehydroepiandrosterone (DHEA), delivered in a sustained manner, individually or in combination, by means of TCPL delivery system on the morphological changes of ventral prostatic tissue. Adult male rats (BW 300-350 gm) were randomly divided into four equal groups. Animals in Group I served as our intact unimplanted controls. Capsules implanted in Group II rats were loaded with TCPL containing 100 mg of DHEA. Rats in Group III were implanted with TCPL loaded with 100 mg of DHEA and 500 mg of DHT, while rats in Group IV were implanted with TCPL loaded with 100 mg of DHEA, 500 mg of DHT and 200 mg of E. Surgical aseptic techniques were performed according to standard laboratory procedures. The animals were maintained at the University of Mississippi Medical Center Animal Facilities following the rules and regulations established by NIH on the Care and Use of Laboratory Animals. At the end of 8 weeks post implantation, all animals were sacrificed and the prostatic tissues were collected, weighed and embedded for histopathological evaluations. Statistical analysis was conducted by using standard computer programs (STATEVIEW, JANDEL, ANOVA at 95% CI). The data obtained in this investigation demonstrated that exogenous intake of E + DHEA + DHT delivered in a sustained manner for eight weeks induced several pathophysiological conditions in ventral prostatic tissue in comparison to prostatic tissue collected from control animals. Cytopathological evaluations of tissue collected from Group II animals demonstrated the following: (i) atrophic pattern of the epithelium, (ii) small, round glands with low cuboidal epithelium, (iii) hypertrophy alone or in conjunction with occasional hyperplasia of the epithelial cells, and (iv) an increased presence of connective tissue stroma. In contrast, ventral prostate collected from animals in Group IV showed an increase in weights of the net prostatic tissues in comparison to the control group. Histopathological observations such as pleomorphism, low cuboidal to pseudostratified glands, prostatic hyperplasia of the epithelial cells, occasional mitotic activity, and occasional presence of connective tissue stroma were detected. In conclusion, the results of this study suggest that the use of TCPL capsules loaded with steroid hormones, individually or in combination can be used to regulate the growth and functional behavior of prostatic tissue in male rodents.