Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina.
BACKGROUND
The mechanisms by which testosterone modulates female genital sexual arousal responses are poorly understood.


OBJECTIVE
To investigate the effects of testosterone on vaginal blood flow and the expression of estrogen and androgen receptor proteins in the rat vagina.


METHODS
Mature female Sprague-Dawley rats were sham-operated (intact) or ovariectomized. Fourteen days after ovariectomy, animals were continuously infused with vehicle or varying doses of testosterone (5.5-55 microg/day). After 2 weeks of treatment, vaginal blood flow in response to pelvic nerve stimulation was measured by laser Doppler flowmetry. Plasma levels of testosterone and estradiol were determined by radioimmunoassay and epithelial thickness was examined in fixed vaginal tissue sections. Androgen and estrogen receptor levels were assessed by equilibrium radioligand binding and by Western blot analyses.


RESULTS
Vaginal blood flow responses were significantly reduced in ovariectomized rats and normalized in animals infused with testosterone. Ovariectomy increased the expression of estrogen receptors and reduced the expression of androgen receptors with no change in receptor-ligand affinity. Testosterone increased the expression of both androgen and estrogen receptors in the vagina. While physiological (11 microg/day) and supraphysiological (55 microg/day) concentrations of testosterone normalized vaginal tissue weight, uterine tissue and whole body weights were not significantly different from ovariectomized rats infused with vehicle. Testosterone infusion, even at supraphysiological concentrations, did not change plasma estradiol levels when compared to vehicle-infused, ovariectomized rats. Likewise, the vaginal epithelium of testosterone-infused rats remained atrophic, similar to vehicle-infused, ovariectomized rats, indicating that testosterone is not aromatized to estrogens at significant levels in the vagina.


CONCLUSIONS
Our data suggest that testosterone regulates androgen and estrogen receptor protein expression in the vagina and enhances vaginal perfusion by an androgen-dependent mechanism. We conclude that testosterone plays an important role in modulating the physiology of the vagina and contributes to improvement of genital sexual arousal responses.
Traish
Abdulmaged M
AM
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA;; Department of Urology, Boston University School of Medicine, Boston, MA, USA.
Kim
Soo Woong
SW
Department of Urology, Seoul National University College of Medicine, Seoul, South Korea.
Stankovic
Miljan
M
Department of Urology, Boston University School of Medicine, Boston, MA, USA.
Goldstein
Irwin
I
Sexual Medicine, Alvarado Hospital, San Diego, CA, USA.
Kim
Noel N
NN
Department of Urology, Boston University School of Medicine, Boston, MA, USA;. Electronic address: nnkim@bu.edu.
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation; D014621:Vagina / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism
D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone