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Endocrine Abstracts (2006) 11 P707


Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes

S Filippi2, A Morelli1, L Vignozzi1, XH Zhang1, M Luconi1, S Donati1, G Forti1 & M Maggi1


1Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy; 2Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, University of Florence, Florence, Italy.

Objectives: Hypogonadism is often associated with diabetes mellitus and both conditions represent major risk factors for erectile dysfunction (ED). The aim of this study was to evaluate the effect of diabetes-induced hypogonadism on ED using two distinct animal models: alloxan-rabbits and streptozotocin (STZ)-rats.

Methods: A subgroup of diabetic animals was Testosterone (T) replaced. After 8 weeks from induction of diabetes, erectile function was evaluated by in vitro contractility studies (rabbit) and in vivo cavernous nerve electro-stimulation (ES, rat).

Results: In both models of chemical diabetes an overt hypogonadism was observed, as derived by the reduced T plasma concentrations and by atrophy of the androgen-dependent accessory glands (prostate and seminal vesicles). In diabetic animals, T substitution completely reverted hypogonadism and diabetes-induced penile hyposensitivity to in vitro (acetylcholine, rabbit) or in vivo (ES, rat) relaxant stimuli. Moreover, T replacement was able to restore nitric oxide synthase (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). The abolishment of the sildenafil effect on erectile response in diabetic animals might be due to the hypogonadism-induced PDE5 deficiency. Accordingly, PDE5 resulted reduced in diabetic STZ-rats (P<0.05) and normalized by T. In STZ-rats, intracavernous injection of sodium nitroprusside (SNP) 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 along with PDE5 expression.

Conclusion: In conclusion, in two experimental models of diabetes T deficiency underlies biochemical alterations leading to ED. Normalizing T in diabetes restores nNOS and PDE5, and reinstates either sensitivity to relaxant stimuli and responsiveness to sildenafil.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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