Growth hormone (GH) is known for its role in the growth of all tissues in the human body. growth hormone) is also a powerful anxiolytic. A study conducted by researchers at the University of São Paulo (USP) deepened the understanding of GH’s ability to reduce anxiety and identified for the first time the population of neurons responsible for modulating the effects of hormones in neuropsychiatric diseases, such as anxiety, depression and post-traumatic Stress.
In the work supported by FAPESP, researchers observed that when the GH receptor was removed from neuronal cells expressing the somatostatin peptide (a growth hormone antagonist), there was an increase in anxiety-like behavior in male mice. The tests also showed a reduction in fear memory in animals of both sexes. The discovery could enable the development of new classes of anxiolytic drugs in the future.
“The discovery of the mechanism involving the anxiolytic action of growth hormone paves the way for a possible – purely chemical – explanation of these disorders and for why these disorders occur more or less frequently in situations with more or less strong growth hormone secretion in individuals .” says José Donato Júnior, professor at the Institute of Biomedical Sciences of the University of São Paulo (ICB-USP) and author of the article published in The Journal of Neuroscience.
In the study, researchers used three types of experiments with mice (open field, elevated plus maze and light-dark box) to test the animals’ ability to explore the environment and put themselves at risk. “These are well-established experiments that measure the animal’s behavior, similar to fear and fear memory (which is behind post-traumatic stress movements). This made it possible to check the effect of the GH hormone on these animals,” explains Donato.
The researcher states that it is not yet known why the study did not show an increase in anxiety-like behavior in female mice. “We think it’s because there is sexual dimorphism. We know that the structure of this area of the brain, where the neurons we study are located, is slightly different in men and women. It’s no coincidence that some disorders are different for men and women,” he says.
The chemical part
Thousands of people worldwide suffer from neuropsychiatric diseases. Although anxiety and depression are among the most common illnesses, the exact cause of these problems is not yet fully understood. It is even believed that it could be a combination of factors such as stress, genetic predisposition, social, economic and gender pressures and others that can contribute to the occurrence of these disorders.
Increasing evidence suggests that hormones may also play an important role in regulating various neurological aspects, altering the predisposition to these disorders. For example, changes in the levels of sex hormones such as estradiol influence anxiety or depressive behavior and fear memory in rodents and humans. Other preliminary studies have shown that glucocorticoids (hormones synthesized from cortisol) may be involved in the development of neuropsychiatric diseases.
At least in the case of GH, the mechanism regulating the hormone in neurons associated with neuropsychiatric diseases had not yet been identified. “We have shown that growth hormone alters the synapse by structurally altering the neurons that secrete somatostatin,” reports the researcher.
In the study, researchers also demonstrated that anxiety disorder, fear memory and post-traumatic stress are different sides of the same neural circuit.
It is worth emphasizing that anxiety can be defined as excessive fear (lack of self-confidence). The fear memory, explains Donato, is related to a negative event that provokes a reaction (a change in the brain), and every time the animal or person is exposed to the same situation again, there can be an exaggerated fear reaction that results from it This can result in paralysis or other symptoms such as excessive crying or shaking.
“All of this happens in the same population of neurons. They are the ones that express the GH receptor, and when we turned off this receptor in our experiment, the animals’ fear memory formation decreased. This means that the ability to form this fear memory is impaired. It may be that growth hormone in post-traumatic stress situations is a contributing factor to the development of these disorders,” he says.
This is because a result of chronic stress increases another hormone called ghrelin – a powerful stimulator of GH secretion. “Ghrelin has long been studied in post-traumatic stress and some studies have shown that exactly this ghrelin-induced GH secretion is increased in chronic stress. This favors the development of memory of fear and post-traumatic stress in the animal’s brain.”
Hormone and prevalence of disorders
In humans, growth hormone is secreted by the pituitary gland and released into the bloodstream, promoting tissue growth throughout the human body through protein formation, cell proliferation, and cell differentiation. It is an essential hormone during the growth phase. Secretion occurs mainly in childhood and adolescence. Secretion peaks also occur during pregnancy. As we age, there is a natural decline in growth hormone.
Problems with its secretion, for example, lead to short stature, which manifests itself primarily from the age of 2 and prevents growth and development in childhood and adolescence.
“Previous studies conducted on people with GH deficiency had already shown a higher prevalence of depression and anxiety in these individuals. However, the cause of this is not yet clear. Some authors attributed this high prevalence to visual and image disturbances mobbing due to short stature,” says Donato.
The researcher emphasizes that the study carried out on mice allows us to verify the key role of growth hormone in the problem, without the influence of other variables, such as image problems. “Through our study we were able to find out to what extent this is a direct effect of the hormone and to what extent it is an indirect effect of the growth deficit. Since we have been able to identify the mechanism in which GH is involved, we know that it is a direct cause of the problem of anxiety disorder and therefore it becomes easier to think about therapies,” he explains.
Donato says the group will now focus growth hormone studies on the period of pregnancy. “During pregnancy a boom by GH. And even after this period, the prevalence of depression – postpartum depression – increases. Of course, there are social, economic and other stresses associated with these types of disruptions. However, we must not forget that these are periods of hormonal boom that can affect the functioning of the brain and lead to these disorders,” concludes the professor.