Tumor necrosis factor-α suppresses the expression of steroid receptor coactivator-1 and -2: A possible mechanism contributing to changes in steroid hormone responsiveness RITA S. LEITE 1 , AMY G. BROWN 1 and JEROME F. STRAUSS, III 2 Center for Research on Reproduction and Women’s Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA 2 Correspondence: Center for Research on Reproduction and Women’s Health, University of Pennsylvania, Philadelphia, PA 19104, USA. E-mail: jfs3@mail.med.upenn.edu <h3>SPECIFIC AIMS</h3> We hypothesized that proinflammatory cytokines may regulate steroid hormone activity in part by altering the levels of nuclear coactivator proteins. We proposed that tumor necrosis factor-α (TNF-α) might decrease coactivator levels in uterine smooth muscle cells (UtSMC), ultimately resulting in decreased progesterone receptor trans -activation. A proinflammatory cytokine-mediated decline in steroid responsiveness in the uterus may play a role in the physiological changes associated with the onset of parturition. <h3>PRINCIPAL FINDINGS</h3> <h3>1. TNF-α decreases SRC-1 and -2 mRNA abundance and protein levels in UtSMC</h3> To pursue the idea that TNF-α administration alters cofactor levels, UtSMC monolayers were treated with TNF-α (10 ng/mL) or diluent and incubated for 0–48 h. After treatment, total RNA was isolated, cDNA synthesized, and quantitative real-time RT-PCR performed. TNF-α did not affect
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