Androgen supplementation in rats increases the inflammatory response and prolongs urethral healing.
OBJECTIVE
To describe the effects of androgens on urethral wound healing, we compared the urethral healing process in castrated Sprague-Dawley rats with and without testosterone supplementation.


METHODS
Of 30 castrated male Sprague-Dawley rats, 15 received testosterone cypionate (3 mg/kg; T+ rats). All rats underwent an urethroplasty procedure and were sacrificed at postoperative days 5, 10, and 20. Neutrophils, macrophages, vessels, myofibroblasts, Ki67+ cells, collagen, and cytokines were quantified with immunofluorescence and real-time polymerase chain reaction.


RESULTS
Penile length was significantly increased in T+ rats (21.8 vs 13.25 mm; P <.001) and operative time decreased (20.8 vs 23.3 minutes; P <.017). On day 5, T+ rats showed elevated neutrophil (727.4 vs 30.75 per high power field; P = .051) and macrophage counts (1295.8 vs 481.5 per high power field; P = .051) compared with those of T- rats. This elevation persisted throughout day 10 (291.7 vs 34; P = .002 and 1283.7 vs 110.2; P = .005) and day 20 (252.7 vs 12.2; P <.001 and 1672.7 vs 115.2; P <.001) reflecting increased and prolonged inflammation. Myofibroblasts were decreased in T+ rats on day 5 (215.7 vs 808.3; P <.001) and increased by day 10 (1490.1 vs 263.0; P = .001) and day 20 (1964.0 vs 210.0; P <.001) consistent with a delayed onset but with prolongation of the proliferative phase. Limitations include the use of castrated rats, which may have been exposed to androgens before castration.


CONCLUSIONS
Testosterone supplementation leads to an increased inflammatory response and myofibroblast proliferation accompanied by prolonged inflammatory and proliferative phases. These novel findings suggest a delayed and possibly impaired urethral healing in the presence of excessive androgens.
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: m-hofer@northwestern.edu.
Matthias D
MD
Hofer
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL.
Earl Y
EY
Cheng
Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Matthew I
MI
Bury
Department of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.
Wei
W
Xu
Department of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.
Seok Jong
SJ
Hong
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
William E
WE
Kaplan
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL; Department of Biomedical Engineering, Northwestern University, Evanston, IL.
Arun K
AK
Sharma
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors; D014521:Urethra / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
D000728:Androgens; D013739:Testosterone