Corticotropin-releasing hormone receptor

Last updated
corticotropin releasing hormone receptor 1
Identifiers
SymbolCRHR1
Alt. symbolsCRHR
NCBI gene 1394
HGNC 2357
OMIM 122561
RefSeq XM_001128344
UniProt P34998
Other data
Locus Chr. 17 q12-q22
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Structures Swiss-model
Domains InterPro
corticotropin releasing hormone receptor 2
Identifiers
SymbolCRHR2
NCBI gene 1395
HGNC 2358
OMIM 602034
RefSeq NM_001883
UniProt Q13324
Other data
Locus Chr. 7 p21-p15
Search for
Structures Swiss-model
Domains InterPro

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). [1] There are two receptors in the family, designated as type 1 and 2, each encoded by a separate gene ( CRHR1 and CRHR2 respectively).

Contents

Function

CRHRs are important mediators in the stress response. [2] 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. [3] 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 of CA1 and CA3. Chronic activation of CRHR1s by CRH induced by early life stress has been shown to underlie memory deficits and learning impairments and anxiety in adulthood.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone 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. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Corticotropin-releasing hormone</span> Mammalian protein found in humans

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in 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.

<span class="mw-page-title-main">Hypothalamic–pituitary–adrenal axis</span> Set of physiological feedback interactions

The hypothalamic–pituitary–adrenal axis is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands. These organs and their interactions constitute the HPA axis.

<span class="mw-page-title-main">Anterior pituitary</span> Anterior lobe of the pituitary gland

A major organ of the endocrine system, the anterior pituitary is the glandular, anterior lobe that together with the posterior lobe 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.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones and a stress hormone. When used as a medication, it is known as hydrocortisone.

Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone, urotensin-I, urocortin, and sauvagine. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRH forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as prohormones.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.

Corticotropes 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.

<span class="mw-page-title-main">Neuropeptide Y</span> Mammalian protein found in Homo sapiens

Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate. 

Urocortin III, a 38–41 amino acid peptide, is a member of the CRF, also known as CRH family of peptides, with a long evolutionary lineage.

<span class="mw-page-title-main">Pituitary adenylate cyclase-activating peptide</span> Protein-coding gene in the species Homo sapiens

Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene. pituitary adenylate cyclase-activating polypeptide is similar to vasoactive intestinal peptide. One of its effects is to stimulate enterochromaffin-like cells. It binds to vasoactive intestinal peptide receptor and to the pituitary adenylate cyclase-activating polypeptide receptor.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 1</span> Protein and coding gene in humans

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.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 2</span> Protein found in humans

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.

<span class="mw-page-title-main">UCN3</span> Protein-coding gene in the species Homo sapiens

Urocortin-3 is a protein that, in humans, is encoded by the UCN3 gene. It belongs to the corticotropin-releasing hormone family.

<span class="mw-page-title-main">Antalarmin</span> Chemical compound

Antalarmin (CP-156,181) is a drug that acts as a CRH1 antagonist.

A Corticotropin-releasing hormone antagonist is a specific type of receptor antagonist that blocks the receptor sites for corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF), which synchronizes the behavioral, endocrine, autonomic, and immune responses to stress by controlling the hypothalamic-pituitary-adrenal axis. CRH antagonists thereby block the consequent secretions of ACTH and cortisol due to stress, among other effects.

Parvocellular neurosecretory cells are small neurons that produce hypothalamic releasing and inhibiting hormones. The cell bodies of these neurons are located in various nuclei of the hypothalamus or in closely related areas of the basal brain, mainly in the medial zone of the hypothalamus. All or most of the axons of the parvocellular neurosecretory cells project to the median eminence, at the base of the brain, where their nerve terminals release the hypothalamic hormones. These hormones are then immediately absorbed into the blood vessels of the hypothalamo-pituitary portal system, which carry them to the anterior pituitary gland, where they regulate the secretion of hormones into the systemic circulation.

Corticotropin-releasing hormone binding protein (CRH-BP) binds corticotropin-releasing hormone (CRH) and several related peptide hormones. It is an ancient, highly conserved protein whose origin predates the divergence of protostomes and deuterostomes.

<span class="mw-page-title-main">Sympathoadrenal system</span>

The sympathoadrenal system is a physiological connection between the sympathetic nervous system and the adrenal medulla and is crucial in an organism's physiological response to outside stimuli. When the body receives sensory information, the sympathetic nervous system sends a signal to preganglionic nerve fibers, which activate the adrenal medulla through acetylcholine. Once activated, norepinephrine and epinephrine are released directly into the blood by postganglionic nerve fibers where they act as the bodily mechanism for "fight-or-flight" responses. Because of this, the sympathoadrenal system plays a large role in maintaining glucose levels, sodium levels, blood pressure, and various other metabolic pathways that couple with bodily responses to the environment. During numerous diseased states, such as hypoglycemia or even stress, the body's metabolic processes are skewed. The sympathoadrenal system works to return the body to homeostasis through the activation or inactivation of the adrenal gland. However, more severe disorders of the sympathoadrenal system such as Pheochromocytoma can affect the body's ability to maintain a homeostatic state. In these cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla.

References

  1. Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM (2003). "International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands". Pharmacol. Rev. 55 (1): 21–6. doi:10.1124/pr.55.1.3. PMID   12615952. S2CID   1572317.
  2. Grammatopoulos DK, Chrousos GP (2002). "Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists". Trends Endocrinol. Metab. 13 (10): 436–44. doi:10.1016/S1043-2760(02)00670-7. PMID   12431840. S2CID   19751772.
  3. Aguilera G, Wynn PC, Harwood JP, Hauger RL, Millan MA, Grewe C, Catt KJ (1986). "Receptor-mediated actions of corticotropin-releasing factor in pituitary gland and nervous system". Neuroendocrinology. 43 (1): 79–88. doi:10.1159/000124513. PMID   3012395.