TUMOR NECROSIS FACTOR REPRESSION OF STEROIDOGENIC GENES

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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.