Elatively low levels,388 and3. MALE REPRODUCTIVE SYSTEM19. THE IMMUNOPHYSIOLOGY OF MALE REPRODUCTIONthere is proof that they respond to LPS by improved expression of inflammatory cytokines, including IL1 and TNF,431,450 it is extremely tough to entirely remove macrophages from Leydig cell preparations. Consequently, it remains unclear no matter whether LPS can regulate Leydig cell steroidogenesis by direct action. Regardless of this uncertainty, there are lots of significant sources of pro-inflammatory molecules within the testis. The testicular macrophages make IL1, TNF, NO, and other ROS, and PGE2 when stimulated by LPS, even though their production capacity is reduced compared with macrophages from other web pages.243,269,270,274,276,277,394,395,464,6 15,645,702 Sertoli cells, peritubular cells, and spermatogenic cells are also possible sources of those pro-inflammatory molecules.369,381,461,615,641 The role of NO as well as other ROS could possibly be particularly critical: treatment of adult mice with LPS causes oxidative harm to Leydig cells, which manifests as a marked reduction of your mitochondrial electrochemical gradient, decreased STAR and HSD3 protein levels, as well as a fall in serum testosterone, related to the effects of oxidation by hydrogen peroxide in Retinoic Acid-inducible Gene-I (RIG-I) Proteins Molecular Weight cultured Leydig cells.65254 Moreover, therapy of rodents with NOS inhibitors counteracts the decrease in serum testosterone levels brought on by stress and sepsis.657,658 Curiously, pretreatment of adult rats using the PTGS2 inhibitor, celecoxib, decreased endogenous intratesticular PGE2 levels, and partially reversed the inhibition of testosterone in response to LPS, without having blocking the improved expression of IL1, TNF, or NOS2 inside the testis.619 An increase in peripheral levels of cytokines from the circulation as a result of activation of macrophages along with other immune cells in the blood and tissues may perhaps also be involved in inhibiting Leydig cell steroidogenesis in the course of LPS-induced inflammation. This may possibly involve exactly the same pro-inflammatory molecules which are made inside the testis following LPS therapy, but potentially other cytokines also. For example, IL2, which is an autocrine T cell growth factor, inhibits gonadotropinstimulated testosterone production by rat Leydig cells in the level of CYP17A,703 but IL2 also stimulates IL1, TNF, and IFN.704,705 The Neural-Immuno-Endocrine Axis in Control of Testicular Steroidogenesis Furthermore to direct effects of inflammatory mediators on the Leydig cells, testicular steroidogenesis is modulated Signal Regulatory Protein Beta Proteins Biological Activity during inflammation by neuroendocrine and neuroimmunological regulatory networks (Figure 19.8). These include the hypothalamic-pituitary-adrenal axis, central control of gonadotropin secretion from the anterior pituitary and neural inputs in to the testis that regulate Leydig cell function by direct action or through adjustments within the testicular vasculature. Activation from the hypothalamic-pituitary-adrenal axis and resulting production of corticosteroids are thekey elements in the regular stress response that, among other items, modulates and limits the severity from the inflammatory response.124,17477 Moreover, corticosteroids inhibit LH and FSH secretion in the pituitary,706 but in addition regulate steroidogenesis straight through precise receptors expressed on the Leydig cell surface,255,707 acting principally by way of suppression in the important steroidogenic enzymes, CYP11A, HSD3 and CYP17A, and induction of Leydig cell apoptosis.192,708,709 The response from the Leydig cells to.
