Identification of genes expressed in the rat prostate that are modulated differently by castration and Finasteride treatment

In mammals, testosterone and 5 alpha-dihydrotestosterone (DHT) are the prin cipal male hormones (androgens). Testosterone is the most abundant circulat ing androgen, and is converted in specific tissues to DHT by the 5 alpha-re ductase enzymes. Although each of these androgens binds to the same recepto r protein (androgen receptor, AR), each exerts biologically distinct effect s. Theories to explain the specific effects of testosterone and DHT have ce ntered an kinetic differences of binding of androgens to the receptor or di fferences in the metabolic fates of he two hormones. In the current experim ents, differential display PCR (ddPCR) was used to identify genes regulated differently by testosterone and DHT. Adult male rats were treated as follo ws: castrated, treated with Finasteride (an inhibitor of 5 alpha-reductase) or left intact for ten days. RNA was prepared from the dissected prostates of these animals and used for ddPCR. Genes exhibiting four distinct patter ns of regulation were observed among the mRNAs. Class 1 genes showed equiva lent expression in intact and Finasteride-treated animals, but were absent in castrated animals (mRNAs D1, D2, D6, D10). Class 2 genes showed higher e xpression in intact animals, intermediate levels following Finasteride trea tment, but were absent in castrated animals (mRNA D8). Two classes of gene were particularly intriguing: class 3 showed gene expression only in the in tact animal (mRNA D7, D9) and class 4 showed increased gene expression foll owing Finasteride treatment (mRNA D3). While the patterns observed for some of these genes (e.g. D8) suggest that the different biological effects of testosterone and DHT may be due to the lower affinity of the AR for testost erone and limiting tissue concentrations of androgen, our results also sugg est that some genes expressed in the rat prostate may be regulated in funda mentally different ways in response to testosterone and DHT.