Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally accepted that androgens are critical for development, growth, and maintenance of penile erectile tissue. However, their role in erectile function, especially in humans, remains controversial. Clinical and preclinical studies have suggested that venoocclusion is modulated by the tone of the vascular smooth muscle of the resistance arteries and the cavernosal tissue and a balance between trabecular smooth muscle content and connective tissue matrix. In men with erectile dysfunction, venous leakage is thought to be a common condition among nonresponders to medical management and is attributed to penile smooth muscle atrophy. In the animal model, androgen deprivation produces penile tissue atrophy concomitant with alterations in dorsal nerve structure, endothelial morphology, reduction in trabecular smooth muscle content, and increased deposition of extracellular matrix. Further, androgen deprivation results in accumulation of fat-containing cells (adipocytes) in the subtunical region of the corpus cavernosum. Androgen deficiency diminishes protein expression and enzymatic activity of nitric oxide synthases (eNOS and nNOS) and phosphodiesterase type 5 (PDE5). The androgen-dependent loss of erectile response is restored by androgen administration but not by administration of PDE5 inhibitors alone. These data suggest that androgens regulate trabecular smooth muscle growth and connective tissue protein synthesis in the corpus cavernosum. Further, androgens may stimulate differentiation of progenitor cells into smooth muscle cells and inhibit their differentiation into adipocytes. Thus, we conclude that androgens exert a direct effect on penile tissue to maintain erectile function and that androgen-deficiency produces a metabolic and structural imbalance in the corpus cavernosum, resulting in venous leakage and erectile dysfunction. .
 ...
PMID:The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. 1642 1

Aging in men is accompanied by a decrease in libido and sexual activity. Recently, it has been demonstrated that a significant proportion of men >60 yr of age has biochemical hypogonadism. Hypoandrogenism, which is associated with other conditions that negatively influence erectile activity, may be an important cofactor in the induction of erectile dysfunction and in the response to phosphodiesterase type 5 (PDE5) inhibitors in aging. In these patients, administration of 50 mg sildenafil or 3 mg apomorphine has no influence on erectile function. Recently we showed that, in hypogonadal subjects, testosterone treatment might stimulate endothelial and neuronal production of vasoactive substances like nitric oxide (NO). Furthermore it can improve endothelial repair mechanisms by increasing bone marrow-derived endothelial progenitor cell (EPC) number in the peripheral circulation. Finally, the normal response to pharmacological stimulation with apomorphine or sildenafil, observed in hypogonadal men treated with testosterone, indicates a positive role of this hormone in the central and peripheral control of erection, confirming the possible positive influence on endothelial function and PDE5 expression. Therefore, we suggest measuring plasma testosterone levels in aged men with erectile dysfunction and recommend treating them barring clinical contraindications. Testosterone plus PDE5 inhibitors may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who were unresponsive to PDE5 inhibitors alone.
 ...
PMID:Erectile dysfunction in aging men: testosterone role in therapeutic protocols. 1676 Jun 37