What is Corticotropin-releasing factor, or CRF?
Corticotropin-releasing factor (CRF, also known as corticotropoin-releasing hormone) is a peptide hormone produced by the hypothalamus in response to stress. It looks like a wound-up cylinder, as shown in the CRF image featuring this article. CRF is best known for its role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for the release of cortisol, a steroid hormone produced by the adrenal gland. Cortisol is important for regulating a wide range of physiological processes, including metabolism, immune function, and the body's response to stress.
CRF acts in the brain by binding to specific receptors located in the hypothalamus and other brain regions, including the amygdala and the hippocampus where it regulates anxiety, fear and memory. The binding of CRF to these receptors activates certain processes in the brain that ultimately lead to the effects of CRF.
The role of CRF in stress responses
CRF is an important mediator of stress responses in the body. When an individual experiences stress, CRF is released into the bloodstream, close to the pituitary gland, where it activates the production of the pituitary hormone ACTH. ACTH, in turn, stimulates the production and release of cortisol by the adrenal glands. Cortisol helps to increase glucose levels in the bloodstream, which provides energy to the body during times of stress. Cortisol also stimulates the liver to produce glucose from stored glycogen, which can be used for energy, and promotes the conversion of amino acids into glucose, which can also be used for energy. This has the advantage that there is no need to eat: focusing on the problem that gives stress comes first, eating comes later.
CRF can also activate the sympathetic nervous system. This allows for the rapid (within seconds) release of adrenaline (US:epinephrine) during stress.
In addition to its role in stress responses, CRF also plays a role in regulating other physiological processes, including fear/anxiety and sleep. CRF has been shown to increase fear and reduce the amount of time spent in deep sleep, all in line with its role in stress responses that are related to fear and anxiety, and staying alert. CRF also plays a role in energy balance.
The mode of action of the CRF system
CRF exerts its effects in the pituitary gland and the brain through binding to two different receptors, creatively named CRF receptor one and two. These receptors are like antenna that are sticking out of the surface of cells. Binding of CRF to its receptors triggers a cascade of events within the cells. This leads to changes in the way these cells function. In the case of stress, the binding of CRF to its receptors in the pituitary gland changes the physiology of some cells so that they start to secrete ACTH.
As CRF has so many effects in the brain, and because it has a prominent role in stress, its actions are under strict control. Having CRF circulating for too long can be detrimental to health. Fortunately, there are two proteins patrolling in the brain that can intercept CRF. These are a shorted form of one of the receptors, and a special protein that binds CRF. Both prevent the binding of CRF to its receptors, so that CRF cannot have an effect when it is not needed.
The effects of chronic CRF exposure on the brain
Chronic exposure to CRF during prolonged stress can have negative effects on the brain, leading to changes in neural circuits and behavior. Chronic exposure to stress and cortisol has been linked to a number of psychiatric disorders, including excessive anxiety and depression.
In detail, research has shown that chronic exposure to stress and cortisol can lead to changes in the structure and function of the hippocampus, a brain region that is important for memory and learning. Chronic stress has been shown to cause dendritic retraction, which is the shrinkage of dendrites, the antenna-like branches of neurons that receive inputs from other neurons. These changes in the hippocampus can result in impairments in memory and learning.
In addition, chronic exposure to CRF and cortisol can lead to changes in the amygdala, a brain region that is important for the regulation of emotional behavior. Chronic stress has been shown to cause an increase in the size of the amygdala, which can result in increased anxiety and fear-related behaviors.
Implications for disease
Given the role of CRF in the regulation of stress responses and the negative effects of chronic exposure to CRF and cortisol on the brain, imbalances in CRF levels can have significant implications for disease. Conditions such as anxiety and depression, which are linked to chronic exposure to stress and cortisol, can have a major impact on health and quality of life.
In addition, imbalances in CRF levels can also contribute to other health problems, such as cardiovascular disease and obesity. Chronic exposure to cortisol can increase blood pressure and heart rate, which can increase the risk of developing heart disease, and can also lead to weight gain and insulin resistance, which can increase the risk of developing type 2 diabetes.
Some effects of CRF
Most of the effects of CRF in the body are linked to stress responses. Other effects of this peptide hormone, and its role in several processes in the brain, the skin, and the immune system, are under heavy scientific investigations. Some of the effects in the brain include:
- Stress response: CRF is a key player in the body's stress response system, stimulating the release of cortisol and other hormones that are essential for the body's stress response.
- Mood regulation: CRF has been linked to depression, anxiety, and other mood disorders. Chronic exposure to high levels of CRF has been shown to contribute to feelings of anxiety, while reducing CRF levels has been shown to improve mood.
- Sleep regulation: CRF has been shown to play a role in regulating sleep-wake cycles. High levels of CRF have been linked to insomnia and other sleep disorders.
- Cognitive function: CRF has been shown to impair cognitive function, particularly memory and learning. Chronic exposure to high levels of CRF has been linked to shrinkage of the hippocampus, an area of the brain responsible for memory and learning.
- Pain perception: CRF has been shown to modulate pain perception, with high levels of CRF being linked to increased sensitivity to pain.
- Appetite regulation: CRF has been shown to play a role in regulating appetite, with high levels of CRF being linked to increased food intake and obesity. This may be particularly important during chronic stress.