Androgen Depletion Augments Antibacterial Prostate Host Defenses in Rats

AMADO A. QUINTAR; CAROLINA LEIMGRUBER ; OSCAR PESSAH; ANDREAS DOLL; CRISTINA A. MALDONADO

INTERNATIONAL JOURNAL OF ANDROLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 35 p. 845 - 859

0105-6263

The defence of the male reproductive tract against microorganisms is critical for fertilization. The prostate gland has been reported to express several moleculesof the innate immune system. However, little information is availableabout how androgens may modulate host defences within the prostate. Wetherefore aimed to examine in the rat the expression of the TLR4 system,which is strongly involved in pathogen recognition, and the secretion of theantibacterial substances rBD-1 and SP-D after androgen withdrawal. Immunoblottingand immunocytochemical analysis revealed a time-dependent increasein these molecules after orchiectomy, with epithelial and stromal cells being animportant source of prostatic host defence proteins. In view of this, we evaluated the potential improvement in antibacterial ability of the prostatic fluid from orchiectomized animals ex vivo. Only samples from rats at 5 days postorchiectomy showed a slight inhibition of Escherichia coli growth. Finally,E. coli was inoculated into the ventral prostate of orchiectomized or control rats, with bacterial growth being counted at 5 days after infection. Animals with androgen depletion presented a lower bacterial count, and showed few histological signs of prostatic inflammation compared with controls. In vitro studies confirmed that isolated lipopolysaccharide (LPS)-treated prostatic cells in the absence of testosterone increased SP-D. Moreover, media from these cells showed a higher antimicrobial activity than supernatants from testosterone-and LPS-treated cells. Our findings indicate that testosterone maintains a reduced expression of key elements for innate immunity and diminishes the antibacterial ability of the rat prostate. These data may represent an important mechanism underlying the immunosuppressive activity of estosterone in the gland. However, this immunosuppressive function of androgens is understandableas a means of avoiding uncontrolled immune responses against the haploid male gamete in the reproductive tract.