Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is produced in response to biological stress, its principal effects are increased production and release of cortisol by the cortex of the adrenal gland. ACTH is related to the circadian rhythm in many organisms. Deficiency of ACTH is a sign of tertiary adrenal insufficiency. Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency when adrenal gland production of cortisol is chronically deficient. In Cushing's disease a pituitary tumor is the cause of elevated ACTH and an excess of cortisol – 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 of the pituitary gland in response to the hormone corticotropin-releasing hormone released by the hypothalamus.
ACTH is synthesized from pre-pro-opiomelanocortin. 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 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 may be cleaved to form α-melanocyte-stimulating hormone.
After a short period of time, ACTH is cleaved into α-melanocyte-stimulating hormone and CLIP, a peptide with unknown activity in humans. Human ACTH has a molecular weight of 4,540 atomic mass units. ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells in the zona fasciculata of the adrenal glands. ACTH acts by binding to cell surface ACTH receptors, which are located on adrenocortical cells of the adrenal cortex; the ACTH receptor is a seven-membrane-spanning G protein-coupled receptor. Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. 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 the P450scc enzyme is located. P450scc catalyzes the first step of steroidogenesis, cleavage of the side-chain of cholesterol.
ACTH stimulates lipoprotein uptake into cortical cells. This increases the bioavailability of cholesterol 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 P450scc, steroid 11β-hydroxylase, their associated electron transfer proteins. This effect is observed over several hours. In addition to steroidogenic enzymes, ACTH enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems; these actions are necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH. As indicated above, ACTH is a cleavage product of the pro-hormone, proopiomelanocortin, which produces other hormones including α-MSH that stimulates the production of melanin. A family of related receptors mediates the actions of these hormones, the MCR, or melanocortin receptor family; these are not associated with the pituitary-adrenal axis. MC2R is the ACTH receptor.
While it has a crucial function in regulating the adrenal, it is expressed elsewhere in the body in the osteoblast, responsible for making new bone, a continual and regulated process in the bodies of air-breathing vertebrates. The functional expression of MC2R on the osteoblast was discovered by Isales et alia in 2005. Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production of VEGF, as it does in the adrenal; this response might be important in maintaining osteoblast survival under some conditions. If this is physiologically important, it 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. While working on her dissertation, Evelyn M. Anderson co-discovered ACTH with James Bertram Collip and David Landsborough Thomson and, in a paper published in 1933, explained its f
This article provides information on candidates who stood for the 1943 Australian federal election. The election was held on 21 August 1943. In 1941, the Lang Labor supporters had rejoined the Australian Labor Party, their seats are still designated as Lang Labor seats. On 16 November 1940, Herbert Johnson was elected to replace Albert Green as the member for Kalgoorlie. On 21 December 1940, Thomas Marwick was elected to replace Henry Gregory as the member for Swan. On 24 May 1941, Grenfell Price was elected to replace John Price as the member for Boothby. On 8 October 1942, Charles Latham was appointed a Western Australian Senator to replace Bertie Johnston. In 1941, Labor MP Maurice Blackburn was expelled from the Labor Party and subsequently sat as an Independent. In 1941, the Australian Labor Party was reabsorbed into the federal Labor Party. Non-Communist members Senator Stan Amour, Senator John Armstrong, Jack Beasley, Dan Mulcahy, Sol Rosevear and Tom Sheehan were all readmitted to the ALP.
In 1943, Country Party MP Thomas Marwick left the party to sit as an Independent. In 1943, Labor Senator Tom Arthur lost his place on the Labor ticket, he contested the election as an Independent. Sir George Bell MP Senator Alexander McLachlan Thomas Paterson MP Sitting members at the time of the election are shown in bold text. Successful candidates are highlighted in the relevant colour. Where there is possible confusion, an asterisk is used. Sitting Senators are shown in bold text. Tickets that elected at least one Senator are highlighted in the relevant colour. Successful candidates are identified by an asterisk. Three seats were up for election; the Labor Party was defending three seats. Labor Senators James Arnold, Bill Ashley and William Large were not up for re-election. Three seats were up for election; the Labor Party was defending three seats. United Australia Party Senators Thomas Crawford and Harry Foll and Country Party Senator Walter Cooper were not up for re-election. Three seats were up for election.
The United Australia Party was defending three seats. United Australia Party Senators James McLachlan, George McLeay and Oliver Uppill were not up for re-election. Three seats were up for election; the Labor Party was defending three seats. United Australia Party Senators John Hayes, Herbert Hays and Burford Sampson were not up for re-election. Three seats were up for election; the Labor Party was defending two seats. The United Australia Party was defending one seat. United Australia Party Senators Charles Brand and John Leckie and Country Party Senator William Gibson were not up for re-election. Four seats were up for election. One of these was a short-term vacancy caused by Country Party Senator Bertie Johnston's death; the Labor Party was defending three seats. The Country Party was defending one seat. United Australia Party Senators Herbert Collett and Allan MacDonald were not up for re-election. 1943 Australian federal election Members of the Australian House of Representatives, 1940–1943 Members of the Australian House of Representatives, 1943–1946 Members of the Australian Senate, 1941–1944 Members of the Australian Senate, 1944–1947 List of political parties in Australia Adam Carr's Election Archive - House of Representatives 1943 Adam Carr's Election Archive - Senate 1943
Castlelost is a civil parish in County Westmeath, Ireland. It is located about 12.81 kilometres south of Mullingar. Castlelost is one of 10 civil parishes in the barony of Fartullagh in the Province of Leinster; the civil parish covers 9,444.4 acres. Castlelost civil parish comprises the village of Rochfortbridge and 16 townlands: Castlelost, Castlelost West, Clontytallon and Kiltotan, Drumman, Gallstown, Gneevebane, Kilbrennan and Collinstown, Piercetown and Rochfortbridge; the neighbouring civil parishes are: Carrick and Pass of Kilbride to the north, Castlejordan to the east, Castlejordan and Newtown to the south and Clonfad to the West. Castlelost civil parish at the IreAtlas Townland Data Base Castlelost civil parish at townlands.ie Castlelost civil parish at the Placenames Database of Ireland