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Corticotropin-releasing hormone

 

 
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Corticotropin-releasing hormone
 
 
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Corticotropin-releasing hormone (CRH), originally named corticotropin-releasing factor (CRF), and also called corticoliberin, is a polypeptide hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
 and neurotransmitter
Neurotransmitter

Neurotransmitters are chemistry which relay, amplify and modulate signals between a neuron and another cell . Neurotransmitters are packaged into vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of...
 involved in the stress response
Stress (medicine)

Stress is a biological term which refers to the consequences of the failure of a human or animal body to respond appropriately to emotional or body threats to the organism, whether actual or imagined....
.

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus
Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
 in response to stress.






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Corticotropin-releasing hormone (CRH), originally named corticotropin-releasing factor (CRF), and also called corticoliberin, is a polypeptide hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
 and neurotransmitter
Neurotransmitter

Neurotransmitters are chemistry which relay, amplify and modulate signals between a neuron and another cell . Neurotransmitters are packaged into vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of...
 involved in the stress response
Stress (medicine)

Stress is a biological term which refers to the consequences of the failure of a human or animal body to respond appropriately to emotional or body threats to the organism, whether actual or imagined....
.

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus
Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
 in response to stress. Marked reduction in CRH has been observed in association with Alzheimer's disease
Alzheimer's disease

Alzheimer's disease , also called Alzheimer disease, Senile Dementia of the Alzheimer Type or simply Alzheimer's, is the most common form of dementia....
, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially-fatal metabolic consequences including hypoglycemia
Hypoglycemia

Hypoglycaemia or hypoglycemia is the medical term for a Pathology state produced by a lower than normal level of Blood glucose. The term hypoglycemia literally means "under-sweet blood" ....
 and hepatitis
Hepatitis

Hepatitis implies injury to the liver characterized by the presence of inflammatory cell s in the Tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation" ....
. In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta
Placenta

The placenta or afterbirth is a highly vascularized ephemeral organ present in Placentalia vertebrates that connects the developing fetal tissues to the uterine wall....
. In the placenta, CRH is a marker that determines the length of gestation
Gestation

Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during mammalian pregnancy can have one or more gestations at the same time ....
 and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, CRH may act as a trigger for parturition.

Hormonal actions

CRH is produced by neuroendocrine cells in the paraventricular nucleus
Paraventricular nucleus

The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes....
 of the hypothalamus
Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
 and is released from neurosecretory terminals of these neurons into the primary capillary plexus of the hypothalamo-hypophyseal portal system. The portal system carries the CRH to the anterior lobe
Anterior pituitary

The anterior pituitary comprises the Anterior#Usage in human anatomy lobe of the pituitary gland and is part of the endocrine system. Unlike the posterior pituitary, the anterior lobe is genuinely glandular, hence the root adeno in its name....
 of the pituitary
Pituitary gland

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g . It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a Dura mater fold ....
, where it stimulates corticotrope
Corticotrope

Corticotropes are cell in the anterior pituitary which produce adrenocorticotrophic hormone and melanocyte stimulating hormone....
s to secrete corticotropin (ACTH) and other biologically-active substances (for example ß-endorphin).

a-helical CRH-(9–41) acts as a CRH antagonist.

Psychopharmacology

The CRH-1 receptor antagonist pexacerfont
Pexacerfont

Pexacerfont is a drug developed by Bristol-Myers Squibb which acts as a Corticotropin releasing hormone receptor 1 antagonist.Corticotropin releasing factor , also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress and drug addiction....
 is currently under investigation for the treatment of Generalized anxiety disorder in women. Another CRH-1 antagonist antalarmin
Antalarmin

Antalarmin is a drug which acts as a Corticotropin releasing hormone receptor 1 antagonist.Corticotropin releasing factor , also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress and drug addiction....
 has been researched in animal studies for the treatment of anxiety, depression and other conditions, but no human trials with this compound have been carried out.

Also, abnormal levels of CRH have been found in the cerebrospinal fluid
Cerebrospinal fluid

Cerebrospinal fluid , Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain....
 of suicide victims.

Recent research has linked the activation of the CRH1 receptor
Corticotropin releasing hormone receptor 1

Corticotropin releasing hormone receptor 1 is a protein, also known as CRF1, with the latter now being the IUPHAR-recommended name....
 with the euphoric feelings that accompany alcohol consumption. A CRH1 receptor antagonist
Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a Receptor , but blocks or dampens agonist-mediated responses....
 developed by Pfizer
Pfizer

Pfizer Incorporated is a major pharmaceutical company, ranking number one in sales in the world. The company is based in New York City, and its research headquarters is in Groton, Connecticut....
, CP-154,526
CP-154,526

CP-154,526 is a potent and selective receptor antagonist of the corticotropin releasing hormone receptor 1 developed by Pfizer.CP-154,526 is under investigation for the potential treatment of alcoholism....
 is under investigation for the potential treatment of alcoholism
Alcoholism

Alcoholism is a term with multiple and sometimes conflicting definitions to describe the detrimental effects of alcohol intake.In common and historic usage, alcoholism refers to any condition that results in the continued consumption of alcoholic beverages despite health problems and negative social consequences....
.

Role in parturition

CRH is also synthesized by the placenta
Placenta

The placenta or afterbirth is a highly vascularized ephemeral organ present in Placentalia vertebrates that connects the developing fetal tissues to the uterine wall....
 and seems to determine the duration of pregnancy
Pregnancy

Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or Multiple birth....
.

Levels rise towards birth and current theory suggests three roles of CRH in parturition:

  • Increases level so dehydroepiandrosterone (DHEA) directly by action on the fetal adrenal gland, and indirectly via the mother's pituitary gland. DHEA has a role in preparing for and stimulating cervical contractions.
  • Increases prostaglandin availability in uteroplacental tissues. Prostaglandins activate cervical contractions.
  • Prior to parturition it may have a role inhibiting contractions, through increasing cAMP levels in the myometrium.


In culture, trophoblast CRH is inhibited by progesterone, which remains high throughout pregnancy. Its release is stimultated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.

Structure

The 41-amino acid
Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
 sequence of CRH was first discovered in sheep by Vale et al in 1981. Its full sequence is:

  • SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA


See also

  • Corticotropin-releasing hormone receptor
    Corticotropin-releasing hormone receptor

    The corticotropin-releasing hormone receptors , otherwise known as corticotropin-releasing factor receptors are a G protein-coupled receptor family that binds corticotropin-releasing hormone....
  • Proopiomelanocortin
    Proopiomelanocortin

    Pro-opiomelanocortin is a precursor polypeptide with 241 amino acid residues.This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as Proprotein convertase....
  • Hypothalamic-pituitary-adrenal axis
    Hypothalamic-pituitary-adrenal axis

    The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis , is a complex set of direct influences and feedback interactions among the hypothalamus , the pituitary gland , and the adrenal glands ....


Further reading