IN-VIVO MANIPULATION (DEPLETION VERSUS ACTIVATION) OF TESTICULAR MACROPHAGES - CENTRAL AND LOCAL-EFFECTS

Testicular macrophages are a relevant cell type for the regulation of Leydig cell steroidogenesis. The availability of liposome technology a llows in vivo manipulation of macrophages in order to analyze their ro le in the regulation of the hypothalamic-pituitary-testicular axis. In this study, adult (70 days of age) and prepubertal (22 days of age) r ats were injected intratesticularly with liposomes containing either d ichloromethylene diphosphonate (C12MDP) to deplete testicular macropha ges or muramyl tripeptide (MTP-PE) to activate them. Control rats were injected with the corresponding volumes of 0.9% NaCl. Animals were ki lled 10 days after treatment. Adult rats injected bilaterally or unila terally with C12MDP liposomes showed increased serum LH and testostero ne concentrations, as well as increased testosterone concentrations in the testicular interstitial fluid. In unilaterally injected rats, tes tosterone concentrations in the interstitial fluid were higher in the macrophage-containing testes than in the contralateral, macrophage-dep leted testes. Adult rats treated bilaterally with MTP-PE liposomes sho wed increased numbers of testicular macrophages, whereas the number of Leydig cells was unchanged. Serum LH concentrations were decreased, b ut no changes were found in testosterone concentrations. Prepubertal r ats treated bilaterally with C12MDP liposomes showed decreased numbers of Leydig cells. However, serum LH and testosterone concentrations we re increased. Otherwise, prepubertal rats treated bilaterally with MTP -PE liposomes showed increased numbers of macrophages and Leydig cells , as well as increased serum testosterone concentrations. These data s uggest that testicular macrophage-derived factors act at two different levels in the pituitary-testicular axis: first, at a central level by inhibiting LH secretion, and secondly, at a local level by stimulatin g Leydig cell steroidogenesis.