| dc.contributor.author | Wright, Alistair Stuart. | en_US |
| dc.date.accessioned | 2014-10-21T12:35:40Z | |
| dc.date.available | 2000 | |
| dc.date.issued | 2000 | en_US |
| dc.identifier.other | AAINQ57375 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55727 | |
| dc.description | Testosterone (T), the major circulating androgen, must be converted to dihydrotestosterone (DHT) by the enzyme 5alpha-reductase (5alpha-R) for maximal activity in the prostate. Based on its higher affinity for the androgen receptor, its high intraprostatic concentration and the observation that men with congenital 5alpha-R deficiency have small prostates, DHT was considered to be the only active androgen in the prostate. In both rats and men, administration of 5alpha-R inhibitors such as finasteride results in prostate shrinkage but not to the same extent as castration. The most probable reason is the reciprocal rise in intraprostatic T that accompanies the decrease in DHT on 5alpha-R inhibition. The objective of the studies presented here was to investigate the relative potencies of T and DHT in prevention of rat ventral prostate regression and in regrowth. | en_US |
| dc.description | To determine the relative potencies of intraprostatic T and DHT in preventing regression, castrated rats were implanted for 4 days with varying sizes of T pellets in the presence or absence of finasteride treatment. In the absence of finasteride, virtually all intraprostatic T was converted to DHT, creating a dose-response for DHT effects in the prostate. In the presence of finasteride, DHT was suppressed to the levels found in a castrated rat and a dose-response for T effects was achieved. Prostate regression consists of atrophy through reduced secretory activity and cell loss through apoptosis. DHT was 2.4 times more potent than T in maintaining normal prostate weight and lumen mass, a measure of epithelial cell function. However, intraprostatic T and DHT were able to inhibit apoptosis with equal potency, indicating that 5alpha-R inhibition in an intact animal results in atrophy and minimal apoptosis because of the potency of intraprostatic T. | en_US |
| dc.description | In order to examine the relative potencies of T and DHT on prostate growth, rats were castrated for 2 weeks to allow the prostate to fully regress and were given T implants in the presence or absence of finasteride to create dose-responses for the effects of intraprostatic T and DHT, respectively. 1.6--1.9 times more T than DHT was needed to achieve half-maximal responses in markers of hypertrophy and hyperplasia and a 2--3 fold higher threshold was observed for T compared to DHT before significant growth occurred. A more pronounced potency difference was found when the relationship between serum T levels and prostate growth examined. 11--16 times more serum T was required for half-maximal prostate growth when DHT formation was blocked by finasteride, suggesting that 5alpha-R plays a role in prostatic androgen accumulation. Whether T or DHT pellets were used to provide the circulating androgen, the concentration of DHT in the ventral prostate in the absence of finasteride was identical, indicating that in terms of prostate physiology, DHT could serve as the major circulating androgen. However, to achieve similar levels of T or DHT in serum, much larger DHT pellets were needed, consistent with the known rapid metabolism of DHT in tissues other than the prostate. | en_US |
| dc.description | Collectively, these results indicate that the role of 5alpha-R in the prostate is two-fold: it converts T to a moderately more potent androgen and permits the accumulation of androgen at low serum T concentrations. T has probably arisen as the major circulating androgen instead of DHT because it can be aromatized to estradiol, which has important roles in male physiology. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2000. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Animal Physiology. | en_US |
| dc.subject | Biophysics, General. | en_US |
| dc.title | The relative potency of testosterone and dihydrotestosterone in the rat ventral prostate: Role of 5alpha-reductase. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
