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04: Growth Hormone and Metabolic Syndrome

Growth Hormone (GH) plays a central role in the growth process and maturation from child to adulthood. GH also has important roles with metabolic syndrome, which is a lifestyle disease. We have interviewed Dr. Shiro Minami, a professor of Bioregulation Department at Institute of Development and Aging Sciences, Nippon Medical School, to find out more on the relationship between GH and metabolic syndrome and its newest research results.

GH is not only for increasing children’s height

The pituitary gland is about a size of a pea (one centimeter in diameter) and is located at the center base of the brain just beneath the hypothalamus. It's often called the "master gland" because it controls secretion of six hormones, which have effects on metabolism, growth and maturation, sexuality and reproduction, and other important bodily functions.

One of the pituitary hormones is Growth Hormone (GH). As you can imagine from its name, GH is a principal hormone that regulates growth, which is critical for body growth in childhood. Like other pituitary hormones, the hypothalamus located just above the pituitary gland, controls the GH secretion. The pattern of GH secretion is very unique. Indeed, the maximum amplitude of GH bursts occurs only a few times a day, for example, at the beginning of the first slow-wave sleep which usually takes place during the first hour of sleep, and at the time when we feel very hungry. Thus once we take in food, the secretion stops.

Also, GH does not only act on bones to make children grow taller. If that were the case, then adults would not need GH. However, GH secretion is present in adults’ bodies, too. In adults, it does not cause growth but it helps to do the followings: 1) To break down fats; 2) To build muscle mass; and 3) To strengthen skin and bones. Also it helps to maintain normal body structure and metabolism, including helping to keep blood glucose levels within set levels. It also acts on kidney to restore water in the body .

Growth Hormone breaks down fat and raises blood glucose level

Here, let’s take a closer look at two of the functions of GH . First is the function of breaking fats and turning them into “ free fatty acids”. Second function is the “glucose metabolism”. As mentioned, GH produces free fatty acids; however, free fatty acids are responsible for insulin resistance. In other words, when GH breaks down fat and increases the amount of free fatty acids, it will impair the function of insulin that leads to the increase of blood glucose level. This condition is called insulin resistance. Indeed, when there is too much GH in the body, insulin resistance is developed resulting in type 2 diabetes. When we are starved, GH has a very important role to raise blood glucose level and to provide enough glucose to body cells. In this sense, GH is considered to be a counter regulator against starvation in human history.

Growth Hormone and Anti-metabolic Effects

On the other hand, when there is an insufficient production of GH, fats will not be broken up, and as a result, will end up accumulating in the body. Hence, your body fat level will increase substantially leading to metabolic syndrome. From these facts, we came to think that there might be a relationship between metabolic syndrome and the shortage of GH. In order to prove our hypothesis, for six weeks we injected GH as supplement to an obese mouse (metabolic-mouse) that had been given high-fat food and observe the effect of GH supplement closely . The results were as predicted. Thanks to injecting GH, in the end, the mouse subcutaneous fat or visceral fat decreased about 30%. Figure4After this experiment, we injected glucose to this same mouse and observed the blood glucose levels in response to glucose injection. Surprisingly, the mouse body was able to decrease the level of blood sugar altogether . This was quite the opposite of what we had known about the rise of GH level. When GH is produced excessively, the free fatty acids increase and insulin resistance takes place resulting in high blood glucose level. Indeed, this was supposed to happen but did not.

Thus, our team decided to do research on how GH works on the function of anti-metabolism and on the improvement of blood glucose level. The following two was what we have found.

First of all, we found out that GH not only decrease the amount of visceral fat but also improve the quality of it. According to our research, GH increases the production of antioxidant enzyme, glutathione peroxidase, which cancels out the oxidant stress that impairs the adipose cells. In addition, we were able to see the increase of Adiponectin in the cells of visceral fat. Adiponectin improves the blood glucose level and is well known to protect one from Atherosclerosis . From these factors, we concluded that by administering GH, we were able to improve the quality of visceral fat.

The second finding was GH could prevent a variety of cell damage. This was especially true with insulin-producing cells in the pancreas. Prevention of damages incurred on insulin-producing cells leads to an improvement of blood glucose regulation by insulin and glucagon, both of which are primary hormones of the pancreas.

Conclusion

In conclusion, from these experiments using metabolic-mouse, we are still in the process of finding how GH acts on anti-metabolism. With proper care and treatment, we are confident that we will be able to prevent the advancement of atherosclerosis and improve the Quality of Life (QOL) in the near future.
We strongly believe that if and when we are able to solve and understand the exact effects of GH, we will clearly know the basic medical reasons for supplementing GH to our patients and this will significantly help us to create effective methods to treat metabolic syndrome in the near future.

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