TUMOR NECROSIS FACTOR REPRESSION OF STEROIDOGENIC GENES

描述：（根据申请人的描述改编）长期 研究的目的是了解通过哪些机制， 免疫系统调节男性生殖功能。 暴露于 细菌内毒素，有一个快速减少，在必要的男性 荷尔蒙睾丸激素 维护所需的TESTON 精子发生和男性的内分泌状态，是由 睾丸间质细胞。 这项工作的重点是阐明 促炎细胞因子、肿瘤坏死因子 因子-α（TNF），抑制睾丸间质细胞睾酮的产生： 特别是，TNF介导的抑制关键睾酮 生物合成酶P450 c17（cyp 17）。 具体目标是：（1）确定 cyp 17启动子中参与cAMP诱导的序列， TNF诱导的cyp 17表达的抑制，和2）鉴定反式作用的cyp 17表达的抑制。 介导cAMP诱导和cyp 17表达的TNF抑制的因子。

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.