Adrenocorticotropic hormone

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Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone (a chain of 10-100 amino acids acting as a chemical messenger) synthesized from a large glycoprotein called pro-opiomelanocortin, or POMC. The main function of ACTH is to stimulate the adrenal glands to release cortisol in response to stress.

ACTH is secreted from the anterior lobe of the pituitary gland in response to the corticotropin-releasing hormone (CRH). In response to stress, CRH is released by the hypothalamus into the hypothalamic-hypophyseal portal system, a modified portion of the circulation that transports neurohormones from the hypothalamus directly to the anterior lobe of the pituitary gland.

ACTH's production, release, and action demonstrate the intricate coordination and complexity of the human body. Under physical or emotional stress, a hormone released from a gland in one part of the body is shunted directly to a gland in another part of the body and stimulates the production of ACTH. In turn, ACTH acts on very specific receptors in another gland to yield cortisol to deal with the stress. And this is just one of many such systems taking place in the body at any one time.

Contents

Structure

ACTH consists of 39 amino acids, the first 13 of which (counting from the N-terminus) may be cleaved to form melanocyte-stimulating hormone α-MSH. α-MSH is a member of a class of peptide hormones, collectively called melanocyte-stimulating hormones (MSH), that are produced by cells of the pituitary gland and stimulate the production and release of melanin by melanocytes in skin and hair. This common structure is one reason that patients with hypocortisolism / Addison's disease, in which ACTH levels are elevated, often present with hyperpigmentation—excessively tanned skin.

The half-life of ACTH in human blood is about ten minutes.

Function

When under stress, there is a release of corticotropin-releasing hormone (CRH) in the hypothalamus. After traveling to the pituitary gland, CRH stimulates the production of ACTH through cleavage of Pro-opiomelanocortin (POMC), a process that also produces melanocyte-stimulating hormone (MSH). ACTH then travels to the adrenal cortex, via the bloodstream, stimulating cortisol to be produced and released. Cortisol then is transported to tissues.

ACTH acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells in the cortex (outer portion) of the adrenal glands. Stimulation of the cortex of the adrenal gland boosts the synthesis of several secretes. The innermost layer of the cortex, the zona reticularis, secretes sex steroids (mostly androgens). The middle portion, the zona fasciculata, secretes mainly glucocorticoids such as cortisol, but also some mineralcorticoids. The zona glomerulosa, the outer layer of the cortex, releases only aldosterone.

With the secretion of ACTH, the hormones lipotropin, melanocyte-stimulating hormone (MSH), β-endorphin, and met-enkephalin are also released. Lipotropin is a major opioid peptide of the human pituitary and is present in concentrations essentially equimolar with corticotropin. β-endorphin is a naturally occurring morphine-like substance. Met-enkephalins are naturally occurring endorphins released from nerve endings of the central nervous system and the adrenal medulla; they act as analgesics and sedatives in the body and appear to affect mood and motivation.

ACTH secretion is related to the circadian rhythm in many organisms with secretion peaking during the morning hours. The secretion of ACTH is controlled by CRH, circadian rhythm, and through negative feedback from blood levels of cortisol and other secretes from the adrenal cortex (Silverthorn 2004). The presence of cortisol inhibits further release of both CRH and ACTH.

Pathologies

Normal values of ACTH in the human body range from 9 to 52 pg/ml (picograms per milliliters). A simple ACTH test can be performed to measure ACTH in the body by analyzing a blood sample. Most accurate results are obtained from tests performed during the morning hours.

Abnormal secretion of ACTH or an abnormal response to the hormone can indicate various pathologies. Greater than normal levels of ACTH may be from hypocortisolism/Addison's disease (due to deficient production of cortisol by the adrenal gland), adrenoleukodystrophy (any of several closely related inheritable disorders, which affect the adrenal glands, nervous system, and testes, and involve the breakdown of certain long chain fatty acids), Cushing's disease, ectopic tumor (tumor outside the pituitary and adrenal glands producing ACTH), or Nelson syndrome (very rare).

Lower than normal ACTH values may be from pituitary deficiency, Cushing's syndrome, an adrenal tumor, or exogenous Cushing's syndrome (Jain 2004).


References

Jain, T. 2004. ACTH. MedlinePlus Medical Encyclopedia.

Silverthorn, D. 2004. Human Physiology, An Integrated Approach (3rd Edition). San Francisco: Benjamin Cummings. ISBN 013102153


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