REGULATION OF GENES BY T AND DHT IN RAT AND HUMAN PROSTA

描述 尽管成人和胎儿睾丸和胎儿产生的主要雄激素 在男性血液中循环的是T，许多组织，如前列腺 腺体，依赖于T向DHT的原位转化。的研究 缺乏催化转化的两种同工酶之一的患者 T对DHT的抑制作用，以及使用特定抑制剂的动物研究 5A-还原酶，已经清楚地证明了T和DHT是不等价的 而DHT的形成在生理上对 腹侧前列腺腺的分化与发育 男性外生殖道的组织。从……的研究中可以清楚地看出 具有雄激素抵抗的动物和人类，T和DHT都与 在靶细胞的细胞核内有相同的受体蛋白。的目标是 这个项目是为了阐明两种雄激素在 发育过程中雄激素作用的总和。两个一般假设 将在拟议的研究中解决：1)T和DHT分别诱导和 前列腺癌分化过程中独特的雄激素反应， 2)DHT的形成是集中雄激素信号所必需的。 分化中的男性泌尿生殖道的一些组织。我们不觉得 一个假说与另一个假说是相互排斥的，事实上， 积累了支持这两种观点的初步数据。拟议的工作是 意义重大。DHT的形成被认为与 几种人类疾病的发病机制，包括良性前列腺增生症、痤疮、多毛症和 男性型秃顶。这些研究的结果将有助于确定 T和DHT在雄激素生理学中的不同作用 有选择地干扰T和T的行为的方向 分布式哈希德可以承受。

DESCRIPTION Although the principal androgen produced by the adult and fetal testis and circulating in the blood of males is T, many tissues such as the prostate gland, are dependent on the in situ conversion of T to DHT. Studies of patients deficient in one of the two isoenzymes that catalyze the conversion of T to DHT, as well as animal studies using specific inhibitors of 5a-reductase, have clearly demonstrated that T and DHT are not equivalent androgens, and that the formation of DHT is physiologically important for the differentiation and development of the ventral prostate gland and tissues of the male external genital tract. It is clear from studies of animals and humans with androgen resistance that both T and DHT bind to the same receptor protein within the nucleus of target cells. The objective of this project is to elucidate mechanisms by which two androgens account for the totality of androgen action during development. Two general hypotheses will be addressed in the proposed studies: 1) T and DHT elicit separate and unique androgenic responses during differentiation of the prostate gland, and 2) DHT formation is necessary to concentrate the androgenic signal in some tissues of the differentiating male urogenital tract. We do not feel that one hypothesis is mutually exclusive of the other, and in fact, have amassed preliminary data that support both. The proposed work is of enormous significance. Formation of DHT has been implicated in the pathogenesis of several human diseases, including BPH, acne, hirsutism, and male pattern baldness. The results of these studies will help define the distinct roles that T and DHT play in androgen physiology and indicate the directions that efforts to selectively interfere with the actions of T and DHT can take.