College of Graduate Studies

UT makes ad­vances in treat­ing sex­ual dys­func­tion


By ERIN SEMPLE | SPECIAL TO THE BLADE
Published on May 1, 2017 | Updated 1:04 a. m.

Erin Semple is an M.D./PhD graduate student at the University of Toledo College of Medicine and Life Sciences.

Sexual dysfunction can be an uncomfortable topic, but if you have experienced it, you are not alone.

Sexual dysfunction occurs in about one-third of men in the United States and worldwide. It is important to understand sexual dysfunction for the purpose of finding treatments.

Erin Semple is an M.D./PhD graduate student at the University of Toledo College of Medicine and Life Sciences.

Men experience sexual dysfunction in many forms. Erectile dysfunction, or the inability to maintain an erection, is common. Some men lack the desire to engage in sexual activity. Others experience premature ejaculation or delayed ejaculation.

Medications such as Viagra are known to help, but in some men, they are ineffective. Viagra and related medications target the blood flow to the penis which is necessary to achieve an erection.

There are not many treatment options for men who have a low desire for sexual activity. Often this problem is secondary to other medications, an unhealthy lifestyle, or mental health problem. Testosterone replacement is used in certain cases for improving sexual desire.

Similarly, men who have either premature or delayed ejaculation have few treatment options. One type of antidepressant known as a selective serotonin reuptake inhibitor has shown promise for treating premature ejaculation in men. Unfortunately, delayed ejaculation is not well-understood, and treatment usually focuses on finding and treating any underlying cause.

Signals from the brain are also known to influence sexual function.

In our lab at the University of Toledo College of Medicine & Life Sciences, formerly the Medical College of Ohio, we study how sexual function is influenced by a hormone in the brain called melanocortin. Melanocortin binds to a protein called the melanocortin 4 receptor (MC4R), which activates many different cells in the brain, called neurons.

Mice also have MC4R in their brains, so they can be used as a model to test how this receptor affects sexual behavior.

When we remove this protein from all neurons of male mice, we find that the mice have difficulty reaching ejaculation. This means that some of the neurons that are activated by melanocortins are important for controlling ejaculation.

 We want to know which neurons are responsible for this behavior, so we selectively restore MC4R in certain populations of neurons in the brain.

We found that restoring these proteins in a very specific region of the brain called the paraventricular nucleus of the hypothalamus (PVN) results in normal ejaculation.

Because sexual function gets worse with age, we also tested these mice as they got older.

We found that older mice without MC4R proteins in their brain are completely unable to reach ejaculation and also have signs of erectile dysfunction.

When we restored these proteins in the PVN, the mice were able to reach ejaculation and no longer had erectile dysfunction.

The results of our studies indicate that melanocortins in the PVN are important for ejaculation, and perhaps erectile function in older mice.

Drugs that increase melanocortins in the brain are being explored as treatments for sexual dysfunction, but there are unwanted side effects such as high blood pressure, increased heart rate, and excessive yawning.

This is because melanocortins act on many different neurons. Imagine a river that flows into multiple smaller streams. This river sends the same water to all of its branches, but only one of the streams leads to the pathway affecting sexual function. If we can increase the flow of that one stream, without affecting the others, we can improve sexual function without unwanted side effects. We have identified that one stream affecting sexual function starts in the PVN of the brain. Now we need to follow that stream to identify even smaller branches that lead to sexual function.

So far, we have found one group of cells in the PVN, called oxytocin neurons, which are involved in sexual behavior. Using the same method as before, we restored MC4R only on oxytocin neurons and found that these mice had normal sexual behavior compared to mice with no MC4R.

Our future goals are to learn how these oxytocin neurons within the PVN are influencing sexual behavior. We may be able to develop therapies with fewer unwanted side effects for men of all ages by continuing our studies to find specific melanocortin cells that are involved in sexual behavior.

Erin Semple is an M.D./​PhD graduate student at the University of Toledo College of Medicine and Life Sciences biomedical science program. She is completing her doctoral studies in the neuroscience and neurological disorders track in the lab of Jennifer Hill. For details email Erin.Semple@rockets.utoledo.edu or go to utoledo.edu/​med/​grad/​biomedical

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