Figure 1. The pathophysiological mechanism of low androgen levels leading to ED. The increased expression of PACS-2 and the decreased expression of A2B, P2X, P2Y, CaM, GIT1, BH4, Hsp-90, and Ng caused by low androgen status inhibit the bio-activity of NOS, leading to endothelial dysfunction and reduced NO production, ultimately causing contraction of smooth muscle cells in penile corpus cavernosum. Low androgen status can directly lead to smooth muscle cell contraction by activating RhoA/Rho kinase. Low androgens status can also promote smooth muscle cell contraction by up-regulating TRPC channel expression and down-regulating TRPV, SKca3, and Ikca channel expression. In addition, low androgen level can cause cellular oxidative stress, apoptosis, pyroptosis, ferroptosis, and tissue fibrosis changes, leading to dysfunction of endothelial cells and smooth muscle cells. Contraction of smooth muscle cells in the penile corpus cavernosum causes ED. ED,Erectile Dysfunction; PACS-2, Phosphofurin acidic cluster sorting protein 2; P1(A2B) and P2 (P2X and P2Y), Purine receptors;CaM, calmodulin;GIT1, G protein-coupled receptor kinase interactor 1; BH4, tetrahydrobiopterin;Hsp-90,heat shock protein-90;Ng, neurogranulin;RhoA,Ras homolog gene family member A; ROCK, Rho-associated coiled-coil kinase;TRPC,Transient receptor potential canonical;TRPV,Transient receptor potential vanilloid; NOS,Nitric Oxide Synthase; NO,Nitric Oxide.
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