Androgen regulation of host defenses and response to inflammatory stimuli in the prostate gland

Abstract

The prostate gland is a strictly androgen-dependent organ which is also the main target of infectious and inflammatory diseases in the male reproductive tract. Host defenses and immunity of the gland have unique features to maintain a constant balance between response and tolerance to diverse antigens. In this context, the effects of reproductive hormones on the male tract are thus complex and have just started to be defined. From the classical description of "the prostatic antibacterial factor," many host defense proteins with potent microbicidal and anti-tumoral activities have been described in the organ. Indeed, it has been proposed a central role for resident cells, that is, epithelial and smooth muscle cells, in the prostatic response against injuries. However, these cells also represent the target of the inflammatory damage, leading to the development of a Proliferative Inflammatory Atrophy-like process in the epithelium and a myofibroblastic-like reactive stroma. Available data on androgen regulation of inflammation led to a model of the complex control, in which the final effect will depend on the tissue microenvironment, the cause of inflammation, and the levels of androgens among other factors. In this paper, we review the current scientific literature about the inflammatory process in the gland, the modulation of host defense proteins, and the influence of testosterone on the resolution of prostatitis.

Inefficient N2-Like Neutrophils Are Promoted by Androgens During Infection

“…The ability of androgens to promote anti-inflammatory/immunomodulatory phenotypes has been previously recognized for professional immune cells ( 16 , 20 ). In general, testosterone tends to inhibit pro-inflammatory molecules such as TNFα, iNOS, and NO whereas induces IL10 and TGFβ1 anti-inflammatory signaling ( 19 , 50 – 52 ).…”

“…Additionally, in monocytes/macrophages, androgens reduce proinflammatory signaling (TLR4, TNFα, IL1β, and IL6) ( 18 ) but enhance anti-inflammatory (IL10) cytokine production ( 19 ). Regarding innate immunity, a few published articles have suggested that testosterone maintains a reduced expression of key elements such as TLRs and modulates the activity of different professional cells ( 18 , 20 ). Nevertheless, the influence of androgen levels on neutrophil activity and plasticity in the initial inflammatory response remains to be investigated.…”

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

“…Like the seminal vesicles, the prostate is a strictly androgen-dependent organ. Testosterone possesses immunosuppressive properties and influences the innate immune responses as well as the outcome of infections and inflammation in the prostate (564). Thus, in rodents and other animals, castration is efficient at eliminating bacterial pathogens and dampening infectionrelated inflammation of the prostate (564).…”

Pathological lesions and global DNA methylation in rat prostate under streptozotocin‐induced diabetes and melatonin supplementation

“…MLT seemed to present a more effective anti‐inflammatory action under hyperglycemic condition, this can be related to the increased uptake of MLT by prostate cells incubated with hyperglycemic medium observed by Hevia et al (). The influence of alterations in androgens levels on the inflammatory response of prostate gland cannot also be discarded (Quintar and Maldonado, ).…”