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Taken from WWW.pubmed.gov (testosterone studies)
J Sex Med. 2006 Mar;3(2):253-64; discussion 264-5, author reply 265-6.
Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct
animal models of chemical diabetes.
· Zhang XH,
· Filippi S,
· Morelli A,
· Vignozzi L,
· Luconi M,
· Donati S,
· Forti G,
· Maggi M.
Andrology Unit, Department of Clinical Physiopathology, Center of Research, Transfer and High Education,
University of Florence, Florence, Italy.
INTRODUCTION: Hypogonadism is often associated with diabetes and both conditions represent major risk
factors for erectile dysfunction (ED). AIM: To investigate the role of hypogonadism on phosphodiesterase
type 5 (PDE5) expression and sildenafil responsiveness in diabetes.
METHODS: Two different models of
experimental diabetes were used: (i) alloxan-induced diabetic rabbit; and (ii) streptozotocin (STZ)-induced
diabetic rat. In both experimental models, animals were separated into three groups: control, diabetic,
diabetic supplemented with testosterone (T) enanthate. Rabbits were used for "in vitro" experiments.
Conversely, each rats group was further subdivided: no further treatment or acute sildenafil dosing
(25 mg/kg, 1 hour before "in vivo" electrical stimulation [ES]).
MAIN OUTCOME MEASURE: Erectile capacity
was evaluated either by "in vitro" contractility study (alloxan-induced diabetic rabbit) and "in vivo"
evaluation of erectile response elicited by ES of cavernous nerve (STZ-induced diabetic rats). Also
endothelial nitric oxide synthase, neural nitric oxide synthase (nNOS), and PDE5 protein (Western blot)
and mRNA (quantitative real-time reverse transcriptase polymerase chain reaction [RT-PCR]) expression were
measured in rat penile samples of each group.
RESULTS: In both models, hypogonadism was observed,
characterized by reduced T and atrophy of androgen-dependent accessory glands. T substitution completely
reverted hypogonadism and diabetes-induced penile hyposensitivity to "in vitro" (acetylcholine, rabbit)
or "in vivo" (ES, rat) relaxant stimuli, along with nNOS expression, which was reduced (P < 0.05) in STZ
rats. In diabetic animals, T substitution reinstated sildenafil-induced enhancement of both "in vitro"
nitric oxide donor (NCX 4040) relaxant effect (rabbit) and "in vivo" ES-induced erection (rat). PDE5 was
reduced in diabetic STZ rats (P < 0.05) and normalized by T. In STZ rats, sodium nitroprusside (SNP)
intracavernous injection induced a more sustained erection than in control rats, which was no further
enhanced by sildenafil. T substitution normalized both hyper-responsiveness to SNP and sildenafil efficacy.
CONCLUSION: In two models of diabetes T deficiency underlies biochemical alterations leading to ED.
Normalizing T in diabetes restores nNOS and PDE5, and reinstates sensitivity to relaxant stimuli and
responsiveness to sildenafil.
PMID: 16490018 [PubMed - indexed for MEDLINE]
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