TUMOR NECROSIS FACTOR REPRESSION OF STEROIDOGENIC GENES

描述：(改编自申请者的描述)长期 这项研究的目的是了解 免疫系统调节男性的生殖功能。在接触到 细菌内毒素，有一种快速下降的必要男性 荷尔蒙，睾丸激素。睾丸激素，这是维持身体健康所必需的 精子发生和男性的内分泌状态，是由 睾丸的间质细胞。这项工作的重点是阐明 促炎症细胞因子、肿瘤坏死的机制 因子-α(TNF)，抑制间质细胞睾酮的产生： 具体地说，肿瘤坏死因子介导的对关键睾酮的抑制 生物合成酶P450c17(CyP17)。具体目标是：1)界定 CYP17启动子中与cAMP诱导有关的序列和 肿瘤坏死因子诱导的细胞色素P17表达抑制，以及2)鉴定反式作用 介导cAMP诱导和肿瘤坏死因子抑制细胞色素P17表达的因素。

DESCRIPTION: (Adapted from the applicant's description) The long term objective of the research is to understand the mechanisms through which the immune system regulates male reproductive function. Following exposure to bacterial endotoxin, there is a rapid decrease in the essential male hormone, testosterone. Testosterone, which is necessary for the maintenance of spermatogenesis and the endocrine status of the male, is produced by the Leydig cells of the testis. The focus of this work is to elucidate the mechanism through which the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF), inhibits Leydig cell testosterone production: specifically, the TNF-mediated inhibition of the key testosterone biosynthetic enzyme, P450c17 (cyp17). The specific aims are: 1) Define the sequences in the cyp17 promoter which are involved in cAMP induction and the TNF-induced repression of cyp17 expression, and 2) Identify the trans-acting factors that mediate cAMP induction and TNF repression of cyp17 expression.