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Modulation of Leydig cell testosterone production by secretory products of macrophages
M Afane1, J J Dubost, B Sauvezie
1Laboratoire de Biologie de la Reproduction et du Developpement, Faculté de Médecine, Clermont-Ferrand, France.
Abstract:
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-1 alpha and interleukin-1 beta 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.
Insights
Testicular macrophages influence Leydig cell testosterone production. Unstimulated macrophages inhibit it, while LPS-stimulated macrophages enhance it, mediated by macrophage secretory products.
Area of Science:
- Reproductive biology
- Immunology
- Endocrinology
Background:
- Leydig cells are crucial for testosterone production.
- Macrophages reside in the testes and can modulate Leydig cell function.
- The role of testicular macrophages in regulating Leydig cell steroidogenesis is not fully understood.
Purpose of the Study:
- To investigate the effect of testicular macrophages on Leydig cell testosterone production.
- To determine the role of macrophage-secreted factors in modulating steroidogenesis.
- To explore the influence of macrophage activation state on Leydig cell function.
Main Methods:
- Primary cultures of rat Leydig cells and testicular macrophages.
- Use of conditioned media from unstimulated and LPS-stimulated macrophages.
- Assays for testosterone production, interleukin-1, and interleukin-6.
- Testing of human monocyte-conditioned media.
Main Results:
- Unstimulated testicular macrophages and their conditioned media inhibited testosterone production in adult rat Leydig cells.
- LPS-stimulated testicular macrophages enhanced testosterone production in both adult and immature rat Leydig cells.
- Interleukin-1 and interleukin-6 were detected in stimulated macrophage supernatants, but were not solely responsible for the observed effects.
- Human monocyte-conditioned media also modulated Leydig cell function.
Conclusions:
- Testicular macrophages modulate Leydig cell steroidogenesis through secreted factors.
- The effect of macrophages depends on their activation state (unstimulated vs. stimulated).
- The stimulatory factors are not species-specific and are distinct from IL-1 and IL-6 alone.