The role of testosterone in erectile physiology: effects of androgens on endothelial progenitor cell generation and function
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For many years, the role of testosterone has been perceived to play a role in the development of prostate cancer and certain cardiovascular diseases (Jones et al., 2013); with its general therapeutic roles being much overlooked. Much of this unprecedented assumption was based upon clinical observations showing the benefit of androgen deprivation in prostate cancer patients, and the perceived reports of higher cardiovascular death amongst people abusing steroid therapies (Jones et al., 2013; Basaria et al., 2010). However, there has been compelling evidence that suggests that testosterone administration within physiological ranges does not contribute to prostate cancer or the pathogenesis of cardiovascular disease (Morgentaler et al., 2009; Jones et al., 2013; Traish et al., 2009). Recent evidence actually suggests the protective role of androgens in the management of metabolic conditions, such as: obesity, metabolic syndrome, and type-2 diabetes mellitus, all of which are known to increase the risk of cardiovascular disease (Traish et al., 2009; Morgentaler et al., 2009; Wang et al., 2000). Erectile dysfunction, which is a type of endothelial dysfunction disorder, is defined as the persistent inability to achieve or maintain an erection for satisfactory sexual performance, and it affects an estimated 30 million American men between the ages of 40 to 70 years old, and this prevalence increases with age (Nehra A, 2007; Barkin J, 2011; Guay A, 2007). The male human erection involves a multifactorial interplay between various mechanisms within the body; encompassing psychological, vascular, neural and endocrine factors (Dean et al., 2005; Castela et al, 2011). The human erection involves the increased inflow of blood into the penile arteries, and the subsequent veno-occlusion, all of which occurs at a perfectly orchestrated hormonal environment (Bivalacqua et al, 1998; Castela et al., 2011). Nitric oxide is released from the endothelium, which dilates penile arteries and relaxes the penile smooth muscles, causing the corpora cavernosa of the penis to fill with blood; the ischiocavernosus and bulbospongiosus muscles then compress the veins, which restricts the egress of blood (Bivalacqua et al, 1998; Castela et al., 2011). Nitric oxide increases cGMP, which decreases intracellular calcium uptake, and increases K+ efflux; these all cause a smooth muscle cell relaxation. The decreased venous outflow from the penis helps maintain erection. In addition to nitric oxide, several other mechanisms are involved in the erectile response. The endothelium, which regulates vascular tone and blood flow, is responsible for the cholinergic smooth muscle relaxation observed by the addition of acetylcholine (Furchgott et al., 1983). Chamness et al. (1995) have shown that androgen differentially affects nitric oxide synthase activity in the male reproductive tract endothelium. Thus, the role of androgens, namely testosterone, is of importance in maintaining erectile function. In addition to affecting nitric oxide synthase activity, testosterone is also shown to affect erectile physiology in many more ways, including its role in activating K+ channels to increase the efflux or inhibit calcium channels via hyperpolarization (Yildiz et al., 2009), and even increasing arterial blood flow to the penis (Aversa et al., 2000). Interestingly, testosterone also modulates endothelial function. Endothelial progenitor cells are responsible for the regeneration of the endothelium. The area of study of these progenitor cells is relatively new, thus, it is important to evaluate how they affect endothelial function. Since erectile dysfunction is a form of endothelial dysfunction, it has been found that patients with erectile dysfunction had significantly lower levels of circulating progenitor cells than patients with a normal erectile function (Baumhäkel et al., 2006). Endothelial cells in the penile arteries play a critical role in regulating the physiological function of the erectile response in humans. Modulation of the endothelium in the penis by androgens, thus, is a critical area of research that must be further addressed.
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