Yesterday I wrote about inflammatory cytokines. Today I will be expanding this work by looking at their role in classical sexual dysfunction. Cytokines play a wide variety of roles in the erectile response. A study by Carneiro et al. (2010) summarizes this well.
A role for cytokines in the pathophysiology of erectile dysfunction (ED) has emerged. Cytokines induce genes that synthesize other peptides in the cytokine family and several mediators, such as prostanoids, leukotrienes, nitric oxide, bradykinin, reactive oxygen species, and platelet-activating factor, all of which can affect vascular function. Consistent with the fact that the cavernosal tissue is a complex extension of the vasculature, risk factors that affect the vasculature have been shown to affect cavernosal function as well.
In this study, titled an “Emerging role for TNF-α in erectile dysfunction”, researchers focused on a cytokine whose increased levels in response to H. Pylori infection I posted about yesterday.
It’s probably best to start with a VERY basic anatomy crash course on the male erection. It can be a bit uncomfortable to think of your penis in this way, so fair warning, this isn’t something for the squeamish.
Probably the simplest (and crudest) analogy I can think of for your penis is as follows:
- Cut a sponge to penis size (Penis tissue)
- Soak the sponge in water (blood)
- Place a condom around your fake dick (skin)
When there is less water (blood) in the sponge (tissue), there is less pressure on the condom (skin), and the penis is flaccid. When there is more blood, there is more pressure, and the penis is erect.
When you are not turned on, the vessels in your penis are constricted. Less blood flows in and the penis is flaccid. This is mediated by Norepinephrine (NE), which works on smooth muscles and contracts those vessels. Nitric Oxide (NO), is basically the anti-NE. It relaxes blood vessels and let’s them dilate. More blood. More boner. It’s interesting to note that much of this is mediated through Ca2+. Higher Ca2+ levels are triggered by NE, and lower Ca2+ levels by NO.
We’re going to jump back to TNF-Alpha.
TNF-Alpha is primarily produced during acute inflammatory reactions. However, its production can also be from bacterial infections or other agents.
Administration of TNF-Alpha in vivo induces impairment of vasodilation and decreases the release of NO. An addition, TNF-Alpha can increase arterial Reactive Oxygen Species (ROS) generation, likely accounting for some of the reduction in NO levels. In addition, eNOS (a variant of NO Synthase) expression is inhibited through reduced the gene promoter activity in response to TNF-Alpha.
(There is some activity at Rho/ROCK level that suggests that TNF-Alpha could cause apoptosis. Maybe this is tied to Dr. Goldstein’s apoptosis/penile scarring theory if you are using the assumption that H. Pylori or an infectious/inflammatory agent is causing increased TNF-Alpha levels. I don’t have the time to go into this today, but may look at it in the future)
In addition TNF-Alpha leads to increased Ca2+ sensitivity (through Rho/ROCK). As noted above, this leads to vasoconstriction – not good for erections.
Increased TNF-Alpha correlates with a higher chance of Erectile Dysfunction (ED), and TNF-Alpha increases with age (a large ED risk-factor).
A mouse model that overexpresses human tumor necrosis factor alpha (hTNF-a) not only exhibits decreased induced erections but also decreased mounting behavior and number of intromissions. Conversely, TNF-a KO mice demonstrate increased number of spontaneous erections.
It is noteworthy that diseases associated with high levels of TNF-a such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and chronic obstructive pulmonary disease also have been associated with ED in males and, in many cases, with sexual dysfunction in females. Although these evidence indicate that TNF-a may be the causal agent of ED, TNF-a is not alone in the list of cytokines, and a myriad of effects must coexist in all of these conditions.
Very interesting. Very interesting indeed.