Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum

Abstract

In men with erectile dysfunction, venous leakage is a common condition among non-responders to medical management and is attributed to penile smooth muscle atrophy. Androgens play a role in regulating trabecular smooth muscle growth and function. Further, androgens stimulate differentiation of progenitor cells into smooth muscle cells and inhibit their differentiation into adipocytes. We postulate that androgens exert a direct effect on penile tissue to maintain erectile function, and that androgen deficiency produces metabolic and structural imbalances in the corpus cavernosum, resulting in venous leakage and erectile dysfunction. To date, research efforts on the mechanisms by which androgens regulate penile erectile physiology have mainly focused on investigating the role of the NO/cGMP pathway. However, androgen-dependent mechanisms that regulate tissue remodeling have been poorly defined. Characterization of the molecular and cellular mechanisms by which androgens regulate corpus cavernosum structural and functional integrity would provide significant gains in knowledge and understanding of an important pathogenic process. In this review, we discuss the potential role of androgen in maintaining differentiation of progenitor cells into smooth muscle lineage and inhibition of differentiation into adipocytes. Androgen deficiency promotes differentiation into adipogenic lineage, and accumulation of adipocytes in the corpus cavernosum may contribute to erectile dysfunction.