Adrenocorticotropic hormone

Adrenocorticotropic hormone (ACTH, also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol by the cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is a sign of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing hormone (CRH)). Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency (e.g. Addison's disease) when adrenal gland production of cortisol is chronically deficient. In Cushing's disease a pituitary tumor is the cause of elevated ACTH (from the anterior pituitary) and an excess of cortisol (hypercortisolism) – this constellation of signs and symptoms is known as Cushing's syndrome. POMC, ACTH and β-lipotropin are secreted from corticotropes in the anterior lobe (or adenohypophysis) of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus. ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC). The removal of the signal peptide during translation produces the 241-amino acid polypeptide POMC, which undergoes a series of post-translational modifications such as phosphorylation and glycosylation before it is proteolytically cleaved by endopeptidases to yield various polypeptide fragments with varying physiological activity. These fragments include: In order to regulate the secretion of ACTH, many substances secreted within this axis exhibit slow/intermediate and fast feedback-loop activity. Glucocorticoids secreted from the adrenal cortex work to inhibit CRH secretion by the hypothalamus, which in turn decreases anterior pituitary secretion of ACTH. Glucocorticoids may also inhibit the rates of POMC gene transcription and peptide synthesis. The latter is an example of a slow feedback loop, which works on the order of hours to days, whereas the former works on the order of minutes. The half-life of ACTH in human blood is about ten minutes. ACTH consists of 39 amino acids, the first 13 of which (counting from the N-terminus) may be cleaved to form α-melanocyte-stimulating hormone (α-MSH). (This common structure is responsible for excessively tanned skin in Addison's disease.) After a short period of time, ACTH is cleaved into α-melanocyte-stimulating hormone (α-MSH) and CLIP, a peptide with unknown activity in humans. Human ACTH has a molecular weight of 4,540 atomic mass units (Da).