Modulation of Leydig cell testosterone production by secretory products of macrophages

Unstimulated macrophages from testes inhibited the production of testosterone by Leydig cells from adult, but not immature, Sprague-Dawley rats (significant after 48 h). Similar results were observed with unstimulated macrophage-conditioned media, suggesting that the observed effect was mediated by one or more secretory products. None of these substances was interleukin-1, since macrophage supernatants tested negative in an interleukin-1α and interleukin-1β sensitive, thymocyte assay. Interleukin-6 was detected by a B cell proliferation assay. After stimulation by LPS, testicular macrophages enhanced testosterone production by Leydig cells from adult and immature rats. This enhancement 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 LPS-stimulated, human monocytes had similar effects on Leydig cells. They were rich in interleukin-1, interleukin-1 receptor antagonist and interleukin-6. The present study suggests that, in adult rats, testicular macrophages modulate Leydig cell steroidogenesis by secretory products whose secretion depends on the physiological state of macrophages. The factor or factors responsible for stimulation are not species-specific. The effect cannot be accounted for by variations in the concentration of the above mentioned interleukins in macrophage supernatants.