Cellular responses to various levels of sustained delivery of testosterone in the ventral prostate.
The objective of this study was to evaluate the effect of various dosages of testosterone (T) delivered in a sustained manner by means of tricalcium phosphate-lysine (TCPL) delivery system on morphological changes of prostatic tissue using adult male rats as a model. In this experiment, adult male rats (250-300 g BW) were randomly divided into five equal groups (n = 8). Rats in group I, II, and III were castrated and implanted subcutaneously with TCPL loaded with three different dosages (10, 100 and 200 mg T, respectively) of T. Rats in group IV were castrated and implanted with sharm TCPL capsules, and rats in group V served as intact unimplanted controls. Surgical aseptic techniques were performed according to standard laboratory procedures. At the end of 4 and 12 weeks post implantation, four animals from each group were sacrificed and the prostate tissues were collected, weighted, and embedded for histo-pathological evaluations. Data collected from this study have shown that exogenous intake of T delivered in a sustained manner for twelve weeks induced several pathophysiological conditions in ventral prostatic tissue in comparison to the control and sham operated groups. This phenomenon was found to be directly proportional to the dose or the level of sustained delivery. The results demonstrated that the use of 10 mg filled TCPL implants decreased the total mass weight of ventral prostate. Light microscopic evaluation of this group (Group I) revealed a cellular adaptation through an atrophy in the epithelium component. Cytopathological observations such as low cuboidal and thin glands, pleomorphism, and occasional presence of connective tissue stroma were detected. In contrast, ventral prostate collected from animals implanted with TCPL filled with 200 mg T (Group III) showed a significant increase in weights of the wet prostatic tissues in comparison to all groups. Histopathological evaluations demonstrated the following. (i) prostatic hypertrophy alone, or in conjunction with hyperplasia of the epithelial cells, (ii) less connective tissue stroma in comparison to the control group, (iii) occasional involvement of mitotic figures, and (iv) increased angiogenesis. No significant change was observed in those animals implanted with TCPL capsules containing 100 mg T compared to the intact control animals.
Cavett
W
W
University of Mississippi Medical Center, Jackson 39216, USA.
Tucci
M
M
Cason
Z
Z
Lemos
L
L
England
B
B
Tsao
A
A
Benghuzzi
H
H
D000818:Animals; D002130:Calcium Phosphates; D002516:Ceramics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D008239:Lysine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010710:Phosphates; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage*
D002130:Calcium Phosphates; D010710:Phosphates; C112656:tricalcium phosphate lysine; D013739:Testosterone; D008239:Lysine