This article is about adrenocorticotropic hormone as a natural hormone. For adrenocorticotropic hormone as a medication and diagnostic agent, seeAdrenocorticotropic hormone (medication).
Deficiency of ACTH is an indicator of secondaryadrenal insufficiency (suppressed production of ACTH due to an impairment of thepituitary gland orhypothalamus, cf.hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release ofcorticotropin releasing hormone (CRH)). Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency (e.g.Addison's disease) when adrenal gland production ofcortisol is chronically deficient. InCushing's disease, a pituitary tumor leads to excessive production of ACTH, which stimulates theadrenal cortex to produce high levels of cortisol.
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 genetranscription 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.
Thehalf-life of ACTH in human blood is reported to be between ten and 30 minutes.[6][7][8]
ACTH influences steroid hormone secretion by both rapid short-term mechanisms that take place within minutes and slower long-term actions. The rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where theP450scc enzyme is located. P450scc catalyzes the first step of steroidogenesis that is cleavage of the side-chain of cholesterol. ACTH also stimulateslipoprotein uptake into cortical cells. This increases thebioavailability ofcholesterol in the cells of the adrenal cortex.
The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, especially P450scc, steroid 11β-hydroxylase, and their associated electron transfer proteins.[11] This effect is observed over several hours.[11]
In addition to steroidogenic enzymes, ACTH also enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems.[12] These actions are probably necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH.[12]
Reference ranges for blood tests, showing adrenocorticotropic hormone (green at left) among the hormones with smallest concentration in the blood
As indicated above, ACTH is a cleavage product of the pro-hormone,proopiomelanocortin (POMC), which also produces other hormones includingα-MSH that stimulates the production ofmelanin. A family of related receptors mediates the actions of these hormones, the MCR, ormelanocortin receptor family. These are mainly not associated with thepituitary-adrenal axis. MC2R is theACTH receptor.[13]
While it has a crucial function in regulating the adrenal glands, it is also expressed elsewhere in the body, specifically in theosteoblast, which is responsible for making new bone, a continual and highly regulated process in the bodies of air-breathing vertebrates.[14] The functional expression of MC2R on the osteoblast was discovered by Isales et alia in 2005.[15] Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production ofVEGF, as it does in the adrenal. This response might be important in maintaining osteoblast survival under some conditions.[16] If this is physiologically important, it probably functions in conditions with short-period or intermittent ACTH signaling, since with continual exposure of osteoblasts to ACTH, the effect was lost in a few hours.
An active synthetic form of ACTH, consisting of the first 23 amino acids of native ACTH, was first made by Klaus Hofmann at theUniversity of Pittsburgh.[19]
DAVID syndrome, a genetic disorder that is characterized by adrenocorticotropic hormone deficiency combined with common variable immunodeficiency and hypogammaglobulinemia.
^Yalow RS, Glick SM, Roth J, Berson SA (November 1964). "Radioimmunoassay of human plasma ACTH".The Journal of Clinical Endocrinology and Metabolism.24 (11):1219–25.doi:10.1210/jcem-24-11-1219.PMID14230021.
^Patel K (1993). "Stability of Adrenocorticotropic Hormone (ACTH) and Pathways of Deamidation of Asparaginyl Residue in Hexapeptide Segments".Stability and Characterization of Protein and Peptide Drugs. Pharmaceutical Biotechnology. Vol. 5. pp. 201–20.doi:10.1007/978-1-4899-1236-7_6.ISBN978-1-4899-1238-1.PMID8019694.
^Zhong Q, Sridhar S, Ruan L, Ding KH, Xie D, Insogna K, et al. (May 2005). "Multiple melanocortin receptors are expressed in bone cells".Bone.36 (5):820–31.doi:10.1016/j.bone.2005.01.020.PMID15804492.
^Collip JB, Anderson E, Thomson DL (August 12, 1933). "The adrenotropic hormone of the anterior pituitary lobe".Lancet.222 (5737):347–348.doi:10.1016/S0140-6736(00)44463-6.
