Corticotropin-releasing Hormone Receptor
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Corticotropin-releasing Hormone Receptor
Corticotropin-releasing hormone receptors (CRHRs), also known as corticotropin-releasing factor receptors (CRFRs) are a G protein-coupled receptor family that binds corticotropin-releasing hormone (CRH). There are two receptors in the family, designated as type 1 and 2, each encoded by a separate gene ( and respectively). Function CRHRs are important mediators in the stress response. Cells in the anterior lobe of the pituitary gland known as corticotropes express the receptors and will secrete adrenocorticotropic hormone (ACTH) when stimulated. This binding of corticotropin releasing-hormone (CRH) activates the hypothalamic-pituitary-adrenal (HPA) axis, one of the two parts of the fight-or-flight response to stress. CRHRs are also present in other brain areas such as the amygdala, locus coeruleus and hippocampus. Within the hippocampus, the CRHR1s are most abundant, residing mainly on the pyramidal cells Pyramidal cells, or pyramidal neurons, are a type of multipolar n ...
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Corticotropin Releasing Hormone Receptor 1
Corticotropin-releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF1, with the latter (CRF1) now being the IUPHAR-recommended name. In humans, CRF1 is encoded by the ''CRHR1'' gene at region 17q21.31, beside micrototubule-associated protein tau MAPT. Structure The human CRHR1 gene contains 14 exons over 20 kb of DNA, and its full gene product is a peptide composed of 444 amino acids. Excision of exon 6 yields in the mRNA for the primary functional CRF1, which is a peptide composed of 415 amino acids, arranged in seven hydrophobic alpha-helices. The CRHR1 gene is alternatively spliced into a series of variants. These variants are generated through deletion of one of the 14 exons, which in some cases causes a frame-shift in the open reading frame, and encode corresponding isoforms of CRF1. Though these isoforms have not been identified in native tissues, the mutations of the splice variants of mRNA suggest the existence of alternate CRF receptors, with differen ...
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Corticotropin Releasing Hormone Receptor 2
Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH. Properties The human CRHR2 gene contains 12 exons. Three major functional isoforms, alpha (411 amino acids), beta (438 amino aci ...
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G Protein-coupled Receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and ...
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Corticotropin-releasing Hormone
Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress (biology), stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the ''CRH'' gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis (HPA axis). Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 196-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress (biological), stress. Increased CRH production has been observed to be associated with Alzheimer's disease and major depression, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypo ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Stress (medicine)
Stress, either physiological, biological or psychological, is an organism's response to a stressor such as an environmental condition. Stress is the body's method of reacting to a condition such as a threat, challenge or physical and psychological barrier. There are two hormones that an individual produces during a stressful situation, these are well known as adrenaline and cortisol. There are two kinds of stress hormone levels. Resting (basal) cortisol levels are normal everyday quantities that are essential for standard functioning. Reactive cortisol levels are increases in cortisol in response to stressors. Stimuli that alter an organism's environment are responded to by multiple systems in the body. In humans and most mammals, the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis are the two major systems that respond to stress. The sympathoadrenal medullary (SAM) axis may activate the fight-or-flight response through the sympathetic nervous system, w ...
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Anterior Pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes, including stress, growth, reproduction, and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels. Structure The pituitary gland sits in a protective bony enclosure called the sella turcica (''Turkish chair/saddle''). It is composed of three lobes: the anterior, intermediate, and posterior lobes. In many animals, these lobes are distinct. However, in humans, the intermediate lobe is but a few cell layers thick and indistinct; as a result, it is often considered part of the anterior pituitary. In all animals, the fleshy, glandular anterior pitui ...
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Pituitary Gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypophysis rests upon the hypophyseal fossa of the sphenoid bone in the center of the middle cranial fossa and is surrounded by a small bony cavity (sella turcica) covered by a dural fold (diaphragma sellae). The anterior pituitary (or adenohypophysis) is a lobe of the gland that regulates several physiological processes including stress, growth, reproduction, and lactation. The intermediate lobe synthesizes and secretes melanocyte-stimulating hormone. The posterior pituitary (or neurohypophysis) is a lobe of the gland that is functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk (also called the infundibular stalk or the infundibulum). Hormones secreted from the pituitary gland ...
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Corticotropes
Corticotropes (or corticotrophs) are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response. Function The primary function of the corticotropic cells is to produce the prohormone POMC in response to the release of CRH from the hypothalamus. POMC is cleaved into several peptide horm ...
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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 an indicator 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 ad ...
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Corticotropin-releasing Hormone
Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress (biology), stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the ''CRH'' gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis (HPA axis). Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 196-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress (biological), stress. Increased CRH production has been observed to be associated with Alzheimer's disease and major depression, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypo ...
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Hypothalamic–pituitary–adrenal Axis
The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a pea-shaped structure located below the hypothalamus), and the adrenal (also called "suprarenal") glands (small, conical organs on top of the kidneys). These organs and their interactions constitute the HPA axis. The HPA axis is a major neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure. It is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome (GAS). While steroid hormones are produced mainly in vertebrates, the physiological role of the HPA axis and corticosteroids in stress response is so fundamental that anal ...
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