Interactions between testicular macrophages and Leydig cells

Abstract

Macrophages enter the testis and proliferate during postnatal maturation, giving rise to an unusually high concentration of cells within the interstitium of the adult testis. Studies conducted in vivo suggest that Leydig cells are involved in regulating the proliferation of macrophages by releasing a mitogen under the regulation of LH. However, it is yet to be determined if this is a direct action. Between postnatal days 20 and 30, macrophages and Leydig cells come into close physical association and form interesting morphological contact sites called digitations of unknown function. Studies conducted in vitro and in vivo indicate that macrophages play an important role in regulating steroidogenesis in Leydig cells by releasing both stimulatory and inhibitory paracrine factors (Fig. 1). The inhibitory factors appear to be those proteins previously characterized in the immune system, such as IL-1 and TNFα, and may be primarily involved in Leydig cell inhibition following immune activation of the macrophages. The stimulatory factor is an unidentified lipophilic factor that acts through a novel StAR-independent pathway. The potential for this stimulatory factor to be of physiological relevance appears to be high in that it can stimulate cultured Leydig cells to produce more testosterone than can LH. Additional studies are needed to determine how these stimulatory and inhibitory factors are synchronized to achieve the regulation of testosterone secretion under both physiological and pathological conditions. It is also yet to be determined how macrophages influence the development and maturation of Leydig cells, as well as how Leydig cells return the favor by influencing the macrophage population to proliferate during postnatal maturation. While most previous studies concerning the regulation of steroidogenesis have focused on endocrine events, it appears that unique and essential paracrine factors with high efficacy have also evolved for the control of this most important process essential to propagation of the species.