Expression of 5Alpha-Reductases and Androgen Receptor mRNA in the Female Prostate of Mastomys.

Prostate growth is primarily dependent on androgen concentrations, the most abundant of which in circulation is testosterone (T). T is converted by 5alpha-reductase type 2 into the most active androgen, 5alpha-dihydrotestosterone (DHT), which interacts with androgen receptors in the prostate. The African rodent, Mastomys [Praomys (Mastomys) Coucha], has been used extensively for biomedical research in the areas of oncology, parasitology and epidemiology. One of the outstanding characteristics of this species is the presence of a well-developed prostate in females. Although the physiological significance of the female prostate in this species has not yet been clearly clarified, the histological characteristics of the gland suggest that it is actively secretory and functional. We previously demonstrated that T stimulates growth of the female prostate and that the DHT concentration in the female prostate is comparable to that observed in males, although serum androgen levels in females are markedly lower. To elucidate the mechanisms and significance of DHT production and accumulation in the female prostate, the mRNA expression of 5alpha-reductase isozymes (type 1, type 2) and androgen receptor in the prostate and other organs was examined in both sexes. 3-4 month-old CHAM strain mastomys were used in this study. cDNA sequences of 5alpha-reductase type 1, type 2 and androgen receptor were determined by 5'- and 3'- rapid amplification of cDNA ends. Real time PCR analysis was performed using a commercial PCR kit containing sybergreen florescent dye in the presence of specific primers. The primers were designed to be specific for the mastomys sequences that were determined in the present study. The highest level of 5alpha-reductase type 1 mRNA expression was observed in the female liver, with moderate levels of expression observed in the male liver, epididymis and ovary. Very low levels were detected in testis and uterus. The level of 5alpha-reductase type 1 expression was very low in the female prostate and was comparable to that observed in the male prostate. Expression of 5alpha-reductase type 2 mRNA was highest in the epididymis, moderate in the male prostate, and absent in the liver, testis, ovary and uterus. Interestingly, the 5alpha-reductase type 2 mRNA was expressed at moderate levels in the female prostate and was comparable to that detected in the male prostate. Androgen receptor mRNA was expressed at high levels in the epididymis, the male prostate and the ovary, with moderate expression observed in the testis and uterus. Also, expression of androgen receptor mRNA was highest in the female prostate, with levels twice that observed in the male prostate. These findings suggest that 5alpha-reductase type 2 is the dominant isozyme associated with the production of DHT in the prostates of both female and male mastomys, and that the high level of androgen receptor expression in the female prostate increases the sensitivity and growth of the female prostate in response to DHT. (poster)