Androgen depletion augments antibacterial prostate host defences in rats.
The defence of the male reproductive tract against microorganisms is critical for fertilization. The prostate gland has been reported to express several molecules of the innate immune system. However, little information is available about how androgens may modulate host defences within the prostate. We therefore aimed to examine in the rat the expression of the TLR4 system, which is strongly involved in pathogen recognition, and the secretion of the antibacterial substances rBD-1 and SP-D after androgen withdrawal. Immunoblotting and immunocytochemical analysis revealed a time-dependent increase in these molecules after orchiectomy, with epithelial and stromal cells being an important 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 post-orchiectomy 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 testosterone in the gland. However, this immunosuppressive function of androgens is understandable as a means of avoiding uncontrolled immune responses against the haploid male gamete in the reproductive tract.
Centro de Microscopía Electrónica, INICSA-CONICET.
A A
AA
Quintar
Centro de Microscopía Electrónica, INICSA-CONICET.
C
C
Leimgruber
Cátedra de Bacteriología y Virología Médicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, X5000HRA, Córdoba, Argentina.
O A
OA
Pessah
Biomedical Research Unit, Research Institute Vall d'Hebron University Hospital, Barcelona, Spain.
A
A
Doll
Centro de Microscopía Electrónica, INICSA-CONICET.
C A
CA
Maldonado
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D011467:Prostate / Q000276:immunology* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar
D000726:Androgen Antagonists