Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors.
BACKGROUND
Type 2 diabetes mellitus (T2DM) has become a major public health issue and is considered a risk factor for erectile dysfunction (ED). T2DM is also associated with androgen deficiency. However, there have been few basic studies on androgen replacement therapy (ART) for ED treatment in T2DM animal models, and the mechanism underlying the effect of ART on T2DM-induced ED is unclear.


OBJECTIVE
To investigate the effect of ART on ED in T2DM rats by examining inflammatory and nitric oxide (NO)-related factors.


METHODS
Otsuka Long-Evans Tokushima Fatty (OLETF) rats and their controls, Long-Evans Tokushima Otsuka (LETO) rats, were distributed into three groups: LETO, OLETF, and ART. In the ART group, OLETF rats were treated daily with testosterone (3 mg/kg/day, subcutaneously) from 20 to 25 weeks of age; LETO and OLETF rats received vehicle only.


METHODS
We measured erectile function by using measurements of the ratio between intracavernosal pressure (ICP) and mean arterial pressure (MAP) following electrical stimulation of the cavernous nerve and by evaluating the endothelial function of the corpus cavernosum in an isometric tension study. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), sirtuin-1 (Sirt1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) mRNA was detected using polymerase chain reaction.


RESULTS
The ICP/MAP ratio in the OLETF group was significantly decreased and that in the ART group was significantly improved (P < 0.01). The response to acetylcholine was significantly decreased in the OLETF group and improved in the ART group (P < 0.01). Although expression of eNOS and Sirt1 mRNA was decreased and that of iNOS, IL-6, and TNF-α mRNA was increased in the OLETF group, ART improved mRNA expression.


CONCLUSIONS
ART suppressed inflammation in rats with T2DM and metabolic disorders and improved their endothelial and erectile functions. ART could be effective for T2DM-induced ED and may be considered a potential ED treatment method.
Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan.
Tomoya
T
Kataoka
Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan.
Yuji
Y
Hotta
Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan.
Yasuhiro
Y
Maeda
Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan; Department of Clinical PharmacyGraduate School of Medical SciencesNagoya City UniversityNagoyaJapan. Electronic address: kkimura@med.nagoya-cu.ac.jp.
Kazunori
K
Kimura
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000378:metabolism; D020318:Rats, Long-Evans; D013739:Testosterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000728:Androgens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C487735:dimethylarginine; D013739:Testosterone; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
Androgen Replacement Therapy; Endothelial Dysfunction; Erectile Dysfunction; Inflammation; Obesity; Testosterone; Type 2 Diabetes Mellitus