Erectile function, a complex neurophysiological process, is dependent upon the health of the penile vascular tissues, nerves and the perineal and ischiocavernosus muscles that support the proximal penis. Adequate arterial inflow and trapping of blood within the cavernosal bodies (veno-occlusion) is critical for the development of increasing pressure and volume expansion. In addition to arterial blood pressure, contraction of the perineal and ischiocavernosus muscles enhances penile rigidity. The veno-occlusive mechanism depends on the integrity of neural, vascular and endocrine systems, as well as the fibro-elastic properties of the cavernosal tissue. Animal studies have shown that androgens play an important role in maintaining penile tissue structure and function and androgen deficiency contributes to veno-occlusive dysfunction. Investigation of androgen action on erectile physiology in the animal model suggest that androgens regulate: a) the expression and activity of nitric oxide synthase isoforms, b) the expression and activity of phosphodiesterases, c) the growth, contractility and state of differentiation of smooth muscle cells, d) connective tissue metabolism, e) the differentiation of progenitor stromal cells into myogenic and adipogenic lineages. We conclude that androgen insufficiency produces erectile dysfunction by affecting multiple cellular components, altering cellular signaling and modulating biochemical pathways, thus adversely changing the structural and functional integrity of penile corpus cavernosum.
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