Alternative names for corticotrophin-releasing hormone

Corticotropin-releasing hormone; corticotrophin-releasing factor; corticotropin-releasing factor; corticoliberin; CRH; CRF 

What is corticotrophin-releasing hormone?

Corticotrophin-releasing hormone is mainly secreted by the paraventricular nucleus of the hypothalamus which, among other functions, releases hormones. Corticotrophin-releasing hormone has several important actions. Its main role in the body is as the central driver of the stress hormone system, known as the hypothalamic–pituitary–adrenal axis. Corticotrophin-releasing hormone is given this name because it stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland (Figure 1). ACTH travels in the bloodstream to the adrenal glands, where it causes the secretion of the stress hormone cortisol.

Corticotrophin-releasing hormone also acts on many other areas within the brain where it suppresses appetite, increases anxiety, and impacts memory and the ability to focus. Together, these effects coordinate behaviour to develop and finetune the body’s response to a stressful experience.

Corticotrophin-releasing hormone is also produced in increasing amounts by the placenta throughout pregnancy. This leads to an increase in cortisol. It is thought that the high levels of corticotrophin-releasing hormone, along with other hormones, are responsible for triggering the start of labour.

Finally, in smaller quantities, corticotrophin-releasing hormone is also made by certain white blood cells, where it stimulates swelling or tenderness known as inflammation, particularly of the gut. 

How is corticotrophin-releasing hormone controlled?

Corticotrophin-releasing hormone secretion is stimulated by nerve activity within the brain. It follows a natural 24-hour rhythm in non-stressed circumstances, where it is highest at around 8 a.m. and lowest at midnight. However, corticotrophin-releasing hormone can also be increased above the normal daily levels by a stressful experience, infection or even exercise. An increase in corticotrophin-releasing hormone leads to higher levels of the stress hormone cortisol which mobilises energy resources needed for dealing with the cause of the stress. High levels of stress hormones over a long period can have negative effects on the body as discussed below. To regulate the hypothalamus–pituitary–adrenal axis, high levels of cortisol block the continued release of corticotrophin-releasing hormone, this is known as a negative feedback loop. 

What happens if I have too much corticotrophin-releasing hormone?

Abnormally high corticotrophin-releasing hormone levels over a prolonged period are linked with a variety of diseases such as clinical depression, anxiety, sleep disturbances and anorexia nervosa.

In addition, high levels of corticotrophin-releasing hormone may worsen inflammatory conditions, including rheumatoid arthritis, psoriasis, ulcerative colitis and Crohn's disease. Initially this might seem unexpected because raised levels of corticotrophin-releasing hormone in the brain can lead to increased glucocorticoids production, and glucocorticoids have an anti-inflammatory effect and are in fact used in the treatment of these conditions. However, research has revealed that when high levels of corticotrophin-releasing hormone occur in tissues outside the brain, they can have a powerful inflammatory action. Increased corticotrophin-releasing hormone levels within the joints, skin or gut can therefore make these inflammatory conditions worse or even play a role in their development. 

What happens if I have too little corticotrophin-releasing hormone?

In people who take high doses of steroids, especially with a prolonged course of treatment, the body’s own production of corticotrophin-releasing hormone, adrenocorticotropic hormone and cortisol can be suppressed. This occurs due to the negative feedback that occurs with taking cortisol-like steroids. In this condition, people may have symptoms of adrenal insufficiency, such as fatigue, weight loss, low blood pressure and nausea. Typically, the symptoms become apparent when the steroid dose is reduced or upon stopping the steroid and patients may require glucocorticoid replacement. Over time, the body may start to produce normal levels of these hormones again, although some people may require lifelong glucocorticoid replacement.

Research has shown that people with Alzheimer’s disease have particularly low corticotrophin-releasing hormone levels. Some scientists have observed a reduced response of the pituitary to corticotrophin-releasing hormone in people with chronic fatigue syndrome, sometimes called myalgic encephalomyelitis, where patients have problems with sleep, memory and concentration, although the evidence between different studies is conflicting. 

During pregnancy, low corticotrophin-releasing hormone production by the placenta or the foetus can result in miscarriage.