MODULATION OF LEYDIG-CELL TESTOSTERONE PRODUCTION BY SECRETORY PRODUCTS OF MACROPHAGES

Unstimulated macrophages from testes inhibited the production of testo sterone by Leydig cells from adult, but not immature, Sprague-Dawley r ats (significant after 48 h). Similar results were observed with unsti mulated macrophage-conditioned media, suggesting that the observed eff ect was mediated by one or more secretory products. None of these subs tances was interleukin-1, since macrophage supernatants tested negativ e in an interleukin-1 alpha and interleukin-1 beta sensitive, thymocyt e assay. Interleukin-6 was detected by a B cell proliferation assay. A fter stimulation by LPS, testicular macrophages enhanced testosterone production by Leydig cells from adult and immature rats. This enhancem ent was dose-dependent and required low concentrations (but over 2.5%) of conditioned media. Interleukin-1 and interleukin-6 activities were detected in LPS-stimulated macrophage supernatants. Supernatants of L PS-stimulated, human monocytes had similar effects on Leydig cells. Th ey were rich in interleukin-1, interleukin-1 receptor antagonist and i nterleukin-6. The present study suggests that, in adult rats, testicul ar macrophages modulate Leydig cell steroidogenesis by secretory produ cts whose secretion depends on the physiological state of macrophages. The factor or factors responsible for stimulation are not species-spe cific. The effect cannot be accounted for by variations in the concent ration of the above mentioned interleukins in macrophage supernatants.