ACTH Receptor
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ACTH Receptor
The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cell plasma membrane, it is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase. The ACTH receptor plays a role in immune function and glucose metabolism. Structure ACTH receptors are the shortest of the melanocortin receptor family and are the smallest known G-coupled receptors. Both human and bovine ACTH receptors are synthesized as 297 residue long proteins with 81% sequence homology. There are currently no available protein X-ray crystallography structures for the ACTH receptor available in the Protein Data Bank; while the ACTH receptor and the β2 adrenergic receptor are relatively distantly-related with a sequence identity of approximately 26%, MC2R investigators such as David Fridmanis have assumed that th ...
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Melanocortin Receptor
Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins: * . MC1R is associated with pigmentation genetics. * . MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone. * . MC3R is associated with childhood growth, accrual of lean mass and onset of puberty. * . Defects in MC4R are a cause of autosomal dominant obesity, accounting for 6% of all cases of early-onset obesity. * . MC5R These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide, and activated by synthetic (i.e. afamelanotide) and endogenous agonist melanocyte-stimulating hormones. Selective ligands Several selective ligands for the melanocortin receptors are known, and some synthetic compounds have been investigated as potential tanning, anti-obesity ...
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Zona Fasciculata
The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fascicles". The ''zona fasciculata'' chiefly produces glucocorticoids (mainly cortisol in humans), which regulate the metabolism of glucose. Glucocorticoid production is stimulated by adrenocorticotropic hormone (ACTH), which is released from the anterior pituitary, especially in times of stress as part of the fight-or-flight response. The ''zona fasciculata'' also generates a small amount of weak androgens (e.g., dehydroepiandrosterone). The main source of androgens will come from the ''zona reticularis'' region. In certain animals such as rodents, the lack of 17alpha-hydroxylase results in the synthesis of corticosterone instead of cortisol. Steroid-producing adrenal tumours and hyperplasia of the ''zona fasciculata'' result in excess corti ...
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Lipolysis
Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important regulatory hormone in lipolysis is insulin; lipolysis can only occur when insulin action falls to low levels, as occurs during fasting. Other hormones that affect lipolysis include glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol. Mechanisms In the body, stores of fat are referred to as adipose tissue. In these areas, intracellular triglycerides are stored in cytoplasmic lipid droplets. When lipase enzymes are phosphorylated, they can access lipid droplets and through multiple steps of hydrolysis, breakdown triglycerides into fatty acids and glycerol. Each step of hydrolysis leads to the removal of one fatty acid. The first step and the rate-limiting step of l ...
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Insulin Resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood, but sulfate depletion may be the important factor. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are ...
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Glucose Metabolism
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms. Carbohydrates are central to many essential metabolic pathways. Plants synthesize carbohydrates from carbon dioxide and water through photosynthesis, allowing them to store energy absorbed from sunlight internally. When animals and fungi consume plants, they use cellular respiration to break down these stored carbohydrates to make energy available to cells. Both animals and plants temporarily store the released energy in the form of high-energy molecules, such as ATP, for use in various cellular processes. Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers (monosaccharides): glucose, fructose, mannose and galactose. After resorption in the gut, the monosaccharides are transported, through the portal vein, to the liver, where all non-glucose monos ...
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Suprachiasmatic Nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons. The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters. Neuroanatomy The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or ''superior'' (hence supra) to the optic chiasm (CHO) bilateral to (on either side of) the third ventricle. The nucleus can be divided into ventrolateral and dorsolateral portions, also known as the core and shell, respectively. These regions differ in their expression of the clock genes, the core expresses them in response to stimuli whereas ...
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Circadian Rhythm
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the environment (Entrainment (chronobiology), entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''wikt:circa#Latin, circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cy ...
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Corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rare case of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency. Roles In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of energy, immune reactions, and stress responses. However, in humans, cortisol is the primary glucocorticoid that is produced primarily in the zona fasciculata of the adrenal cortex. Corticosterone has only weak glucocorticoid and mineralocorticoid potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. Corticosterone is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. Glomerulosa cells are found in th ...
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Cellular Differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Although metabolic composition does get altered quite dramaticall ...
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Adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types. There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT), which are also known as white and brown fat, respectively, and comprise two types of fat cells. Structure White fat cells White fat cells contain a single large lipid droplet surrounded by a layer of cytoplasm, and are known as unilocular. The nucleus is flattened and pushed to the periphery. A typical fat cell is 0.1 mm in diameter with some being twice that size, and others half that size. However, these numerical estimates of fat cell size depend largely on the measurement method and the location of the adipose tissue. The fat stored i ...
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Angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys. An oligopeptide, angiotensin is a hormone and a dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. Angiotensin was isolated in the late 1930s (first named 'angiotonin' or 'hypertensin') and subsequently characterized and synthesized by groups at the Cleveland Clinic and Ciba laboratories. Precursor and types Angiotensinogen Angiotensinogen is an α-2-globulin synthesized in the liver and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides. It is a member of the serpin family of proteins, leading to another name: Serpin A8, although it is not known ...
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Zona Glomerulosa
The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin for "ball"). In response to increased potassium levels, renin or decreased blood flow to the kidneys, cells of the ''zona glomerulosa'' produce and secrete the mineralocorticoid aldosterone into the blood as part of the renin–angiotensin system.Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14 Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca2+ channels, isolated ''zona glomerulosa'' cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry. However, mouse ''zona glomerulosa'' cells within adrenal slices spontaneously generate membrane potential oscillations of low per ...
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