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In vivo manipulation (depletion versus activation) of testicular macrophages: central and local effects
Abstract:
Testicular macrophages are a relevant cell type for the regulation of Leydig cell steroidogenesis. The availability of liposome technology allows in vivo manipulation of macrophages in order to analyze their role in the regulation of the hypothalamic-pituitary-testicular axis. In this study, adult (70 days of age) and prepubertal (22 days of age) rats were injected intratesticularly with liposomes containing either dichloromethylene diphosphonate (C12MDP) to deplete testicular macrophages or muramyl tripeptide (MTP-PE) to activate them. Control rats were injected with the corresponding volumes of 0.9% NaCl. Animals were killed 10 days after treatment. Adult rats injected bilaterally or unilaterally with C12MDP liposomes showed increased serum LH and testosterone concentrations, as well as increased testosterone concentrations in the testicular interstitial fluid. In unilaterally injected rats, testosterone concentrations in the interstitial fluid were higher in the macrophage-containing testes than in the contralateral, macrophage-depleted testes. Adult rats treated bilaterally with MTP-PE liposomes showed increased numbers of testicular macrophages, whereas the number of Leydig cells was unchanged. Serum LH concentrations were decreased, but no changes were found in testosterone concentrations. Prepubertal rats treated bilaterally with C12MDP liposomes showed decreased numbers of Leydig cells. However, serum LH and testosterone concentrations were 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 suggest 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 stimulating Leydig cell steroidogenesis.
Insights
Testicular macrophages regulate Leydig cell steroidogenesis. Manipulating these cells with liposomes (dichloromethylene diphosphonate or muramyl tripeptide) impacts testosterone and LH levels in adult and prepubertal rats.
Area of Science:
- Reproductive Endocrinology
- Cell Biology
- Immunology
Background:
- Testicular macrophages play a role in Leydig cell steroidogenesis.
- Liposome technology enables in vivo manipulation of macrophages.
Purpose of the Study:
- To investigate the role of testicular macrophages in regulating the hypothalamic-pituitary-testicular axis.
- To analyze the effects of macrophage depletion and activation on steroidogenesis.
Main Methods:
- Adult and prepubertal rats were injected intratesticularly with liposomes containing dichloromethylene diphosphonate (C12MDP) to deplete macrophages or muramyl tripeptide (MTP-PE) to activate them.
- Control groups received saline injections.
- Serum and testicular interstitial fluid were analyzed 10 days post-treatment.
Main Results:
- In adult rats, C12MDP treatment increased serum LH and testosterone. MTP-PE treatment increased macrophage numbers but decreased serum LH.
- In prepubertal rats, C12MDP treatment increased serum LH and testosterone despite decreased Leydig cells. MTP-PE treatment increased macrophages, Leydig cells, and serum testosterone.
- Macrophage manipulation influenced both central (LH secretion) and local (steroidogenesis) regulation.
Conclusions:
- Testicular macrophages influence the pituitary-testicular axis at central and local levels.
- Macrophage-derived factors can inhibit LH secretion and stimulate Leydig cell steroidogenesis.