Avila D M, Fuqua S A, George F W, McPhaul M J
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-8857, USA.
J Endocrinol. 1998 Dec;159(3):403-11. doi: 10.1677/joe.0.1590403.
In mammals, testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens). Testosterone is the most abundant circulating androgen, and is converted in specific tissues to DHT by the 5alpha-reductase enzymes. Although each of these androgens binds to the same receptor protein (androgen receptor, AR), each exerts biologically distinct effects. Theories to explain the specific effects of testosterone and DHT have centered on kinetic differences of binding of androgens to the receptor or differences in the metabolic fates of the two hormones. In the current experiments, differential display PCR (ddPCR) was used to identify genes regulated differently by testosterone and DHT. Adult male rats were treated as follows: castrated, treated with Finasteride (an inhibitor of 5alpha-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 patterns of regulation were observed among the mRNAs. Class 1 genes showed equivalent expression in intact and Finasteride-treated animals, but were absent in castrated animals (mRNAs D1, D2, D6, D10). Class 2 genes showed higher expression in intact animals, intermediate levels following Finasteride treatment, but were absent in castrated animals (mRNA D8). Two classes of gene were particularly intriguing: class 3 showed gene expression only in the intact animal (mRNA D7, D9) and class 4 showed increased gene expression following 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 testosterone and limiting tissue concentrations of androgen, our results also suggest that some genes expressed in the rat prostate may be regulated in fundamentally different ways in response to testosterone and DHT.
在哺乳动物中，睾酮和5α-二氢睾酮（DHT）是主要的雄性激素（雄激素）。睾酮是循环中含量最丰富的雄激素，在特定组织中通过5α-还原酶转化为DHT。尽管这些雄激素都与相同的受体蛋白（雄激素受体，AR）结合，但各自发挥着生物学上不同的作用。解释睾酮和DHT特定作用的理论主要集中在雄激素与受体结合的动力学差异或两种激素代谢命运的差异上。在当前实验中，差异显示PCR（ddPCR）被用于鉴定受睾酮和DHT不同调控的基因。成年雄性大鼠接受如下处理：去势、用非那雄胺（一种5α-还原酶抑制剂）处理或保持完整状态10天。从这些动物解剖得到的前列腺中提取RNA，并用于ddPCR。在mRNA中观察到呈现四种不同调控模式的基因。第1类基因在完整和非那雄胺处理的动物中表达相当，但在去势动物中缺失（mRNA D1、D2、D6、D10）。第2类基因在完整动物中表达较高，非那雄胺处理后表达水平中等，但在去势动物中缺失（mRNA D8）。有两类基因特别引人关注：第3类基因仅在完整动物中显示基因表达（mRNA D7、D9），第4类基因在非那雄胺处理后显示基因表达增加（mRNA D3）。虽然观察到的其中一些基因（如D8）的模式表明，睾酮和DHT不同的生物学效应可能是由于AR对睾酮的亲和力较低以及雄激素的组织浓度受限，但我们的结果也表明，大鼠前列腺中表达的一些基因可能以根本不同的方式响应睾酮和DHT进行调控。
