Dihydrotestosterone Exerts a Depressive Influence on the Production of Interleukin-4 (IL-4), IL-5, and y-Interferon, But Not IL-2 by Activated Murine T Cells

The present study examined the effects of the androgen steroid, dihydrotestosterone (DHT), on murine T-cell production of a number of lymphokines. Direct exposure of murine T cells to DHT in vitro was found to reduce the amount of interleukin-4 (IL-4). IL-5, and y-interferon (ylFN) produced after activation with anti-CD3 without affecting the production of IL-2. Exposure of T cells to either androstenedione or testosterone (the metabolic precursors of DHT) affected no change in the biosynthesis of either of these lymphokines. We have determined that macrophages possess Ba-reductase, and are thus competent to metabolize testosterone to DHT. This physicochemical information is complemented by a functional analysis of macrophage metabolism of testosterone. By incubating bone marrow macrophages with testosterone, before their use as accessory cells, the IL-4 and IL-5 producing potential of the activated T cells cocultured with them was depressed. That the observed effect was mediated by the conversion of testosterone to DHT was further corrob-