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Journal of Andrology, Vol. 27, No. 4, July/August 2006
Copyright © American Society of Andrology

Dose–Response Relationship Between Testosterone and Erectile Function: Evidence for the Existence of a Critical Threshold

NOEL N. KIM

IRWIN GOLDSTEIN

ABDULMAGED M. TRAISH^,

From the ^* Department of Urology, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey; and the Departments of Urology and Biochemistry, Boston University School of Medicine, Boston, Massachusetts.

Correspondence to: Abdulmaged M. Traish, Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, 700 Albany St., Rm. W607D, Boston, Massachusetts 02118 (e-mail: atraish{at}bu.edu).

Androgens play an important role in erectile function. However, the dose–response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 µg/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 µg/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 ± 0.12 ng/mL (1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 ± 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%–12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.

     Key words: Androgens, erection, neural NOS, phosphodiesterase type 5, prostate

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