Impotence occurs in 50% of diabetic men, an incidence four to five fold that seen in the normal male population. There is no current effective treatment for this disorder nor clear understanding of its etiology. Utilizing the Streptozotocin induced diabetic male rat (SIDMR) we have presented morphological and endocrine evidence to support a primary disorder of Leydig cells in this diabetic animal model. Recent studies extending this hypothesis have revealed limitations of the animal model (SIDMR) for further study. More recently we have described morphological and preliminary endocrine data to support a similar hypothesis in the """"""""BB"""""""" rat a model of Type I diabetes, partly developed by this investigator. We will further characterize this animal model with more extensive evaluation of the pituitary testicular axis between 6 and 12 months of age where both Leydig and Sertoli cell dysfunction has been demonstrated to occur. Androgen biosynthetic pathways will be determined in testicular tissues of these animals to identify the site of enzymatic blockade. Sexual behavioral studies and their relation to gonadal hormones, morphology and enzymology in tests will be evaluated. Normalization of glucose using implantable pumps for insulin delivery will be used to determine reversibility of gonadal dysfunction. We have recently discovered endocrine and morphological evidence in impotent diabetic man which parallel findings in the diabetic animal model. These include increased urinary LH, altered circadian rhythms of both free and total testosterone, and blunted free testosterone responses to HCG. All these subjects had organic impotence on the basis of nocturnal penile tumescence studies. Preliminary data using home-glucose monitoring and testosterone therapy suggest reversibility is possible in select individuals. We plan to extend this study to include a group of age-matched impotent diabetics with normal sexual function. Angiography studies of the internal pudendal arteries and morphometric evaluation of testicular vessel diameter in biopsy tissue will be done to determine if vascular insufficiency contributes to this disorder.
