One may expect that an increase in ACTH would encourage thymocyte steroidogenesis, as it does in the adrenal gland, and that, if the system were effective, it would result in thymus involution. ACTH, on the other hand, increases the production of steroidogenic enzymes as well as the proliferation of steroidogenic adrenal cells. This indicates that, under normal conditions, the thymus is able to prevent its own atrophy by inhibiting hormone production itself.
The thymus continues to produce hormones even after birth. The amount produced decreases but it remains detectable in older individuals. However, the thymus also begins to shrink at this time; therefore, the overall effect is one of atrophy. This process is called "thymic senescence" and it is responsible for reducing the immune response to infections. People who have undergone cardiac surgery or who have been exposed to large amounts of radiation therapy can develop severe infections later in life, which might be fatal if they did not have a strong immune system. In such cases, treatment with ACTH restores the immune response weakened by the surgery or radiation therapy.
ACTH has many effects on the body. It promotes the release of steroids from the adrenals and reproductive organs. It also stimulates bone marrow production of red blood cells and white blood cells. Finally, it affects certain cells in the brain that control emotion and behavior. Studies have shown that people with depression benefit from treatments with ACTH.
Under normal settings, adrenocorticotropic hormone can promote aldosterone production rapidly and transiently, albeit to a smaller amount than angiotensin II and potassium. Furthermore, ACTH promotes the synthesis of aldosterone both abruptly and chronically. Abrupt increases in ACTH levels such as those seen in patients with Cushing's syndrome will result in increased aldosterone production and secretion.
Chronic increases in ACTH lead to increased aldosterone production by the adrenal cortex. This effect is mediated through the activation of transcription factors called nuclear receptors that regulate the expression of genes involved in aldosterone production and secretion. Activation of these receptors leads to increased activity of enzymes required for aldosterone production including steroid sulfotransferases, UDP-glucuronosyltransferases, and 17α-hydroxylase/C17,20-lyase. These enzymes are responsible for converting inactive precursors into active forms of aldosterone. Thus, chronic ACTH stimulation results in increased aldosterone production due to increased mRNA transcription and protein translation of these enzymes.
A study conducted by Zuckerman et al. (2001) examined the effects of acute and chronic administration of ACTH on aldosterone production in rats. They found that acute injection of ACTH significantly increased plasma aldosterone concentrations within 30 minutes and this increase remained elevated for 3 hours after injection.
The hypothalamus and pituitary glands in the brain interact with the adrenal glands. The hypothalamus is responsible for the production of corticotropin-releasing hormone (CRH). This stimulates the pituitary gland, causing it to produce adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands, causing them to produce and release corticosteroid hormones into the bloodstream. When the body is exposed to a stress factor such as a shock or fear, the hypothalamus releases CRH rapidly. This causes the pituitary gland to release more ACTH which in turn causes the adrenal glands to release more cortisol or other corticosteroids.
Cortisol helps the body deal with stress by increasing blood flow to major organs including the heart, lungs, and muscles. If excessive amounts of cortisol are released over time, this can have negative effects on the skin, immune system, mental state, and metabolism. Stress can also cause the hypothalamus to release epinephrine (adrenaline) and norepinephrine which have similar effects to cortisol but last longer.
Adrenal fatigue can occur when the adrenals are overloaded with stressors for long periods of time. This can lead to decreased production of cortisol and other hormones produced by the adrenal glands. Symptoms include poor memory, depression, weight gain, weakness, pain, and many other issues related to the musculoskeletal system.
In severe cases, the adrenal glands can shrink due to chronic stress.
Adrenocorticotropic hormone (ACTH) is a hormone that promotes cortisol production. Cortisol is a steroid hormone produced by the adrenal glands that regulates glucose, protein, and lipid metabolism, suppresses the immune system's reaction, and aids in blood pressure regulation. By stimulating the production of cortisol, ACTH helps the body respond appropriately to stress.
How does it help the body respond appropriately to stress? When you are stressed, your brain sends out signals called corticosteroids. These hormones regulate many different functions in the body, such as growth, cognition, fat distribution, energy levels, and the immune system. Too much or too little cortisol can be harmful. Healthy people need stable levels of this hormone to function properly. People with Cushing's disease have chronically high levels of cortisol due to excessive secretion from the pituitary gland. Those with Cushings syndrome develop excess skin folds, abdominal fat, and bone mass due to increased cortisol levels over a long period of time. Those who suffer from depression may have low levels of cortisol at rest, which improves with exercise or other forms of physical activity.
People with Cushing's disease need immediate treatment to reduce the risk of developing heart disease and diabetes. They are also treated with drugs to lower their blood sugar and cholesterol levels. People with Cushings syndrome need treatment only if they show signs of hypercortisolism (excessive secretion of cortisol).
The adrenal cortex is then stimulated by ACTH to create the hormone cortisol. This approach will be covered in greater depth further down. The adrenal medulla is a neuroendocrine tissue made up of neurons from the postganglionic sympathetic nervous system (SNS). The medulla oblongata is the lower brainstem region where the adrenal glands are located. The medulla controls the secretion of adrenaline and noradrenaline by the adrenal gland. It does this by sending chemical messages directly to the cells. These messages trigger the release of hormones into the blood.
When stress occurs, increased levels of ACTH are released from the anterior pituitary gland. This causes the adrenal cortex to produce more cortisol. Cortisol binds to receptors on cells all over the body, causing them to respond by increasing blood flow, mobilizing energy stores, and preparing the body for action or escape. For example, when faced with a threat, adrenaline is released from the adrenal medulla causing heart rate to increase, breathing to become deeper, and blood to be diverted from non-essential organs such as the gut to provide energy to the muscles. This prepares us for fight or flight.
Cortisol also has negative effects during stress. It leads to changes that make it harder for the body to cope with future stresses by reducing the immune system, causing insulin resistance, and altering pain perception. High levels of cortisol have been linked to depression and anxiety.
Corticotropes of the anterior pituitary gland produce and release ACTH. This hormone's target tissue is the adrenal cortex. To fully grasp this notion, consider the hormone's name: adren/o = adrenal gland; cortico = cortex (cortex = outer covering); tropic = trophic hormone. Thus, ACTH stimulates the development and function of all three zones of the adrenal cortex.
ACTH acts on cells that it contacts. It does not spread through the body. Therefore, if you were to inject yourself with ACTH, the only place it would have effect is on tissues near where you injected it. In fact, because it doesn't spread, too much ACTH can be toxic to other parts of the body. The dose of ACTH that can be given intravenously is much higher than the dose that can be given by injection into a single site. As well, intramuscular injections of ACTH can cause inflammation at the site of injection.
ACTH promotes the synthesis and secretion of glucocorticoids from the adrenal cortex. Glucocorticoids are steroid hormones that regulate blood glucose levels, salt balance, and protect the brain from stress. They are also involved in immune response, bone health, skin health, and reproductive ability.
Glucocorticoid activity is controlled by the hypothalamic-pituitary-adrenal axis.