Target type: molecularfunction
Binding to corticotropin-releasing hormone, a polypeptide hormone involved in the stress response. It is released by the hypothalamus and stimulates the release of corticotropin by the anterior pituitary gland. [PMID:7556876]
Corticotropin-releasing hormone (CRH) binding is a crucial step in the hypothalamic-pituitary-adrenal (HPA) axis, a critical stress response system in mammals. CRH, a peptide hormone synthesized and secreted by the paraventricular nucleus of the hypothalamus, plays a central role in activating the HPA axis.
CRH binding to its receptor, the CRH receptor 1 (CRHR1), initiates a cascade of molecular events that ultimately lead to the release of cortisol (in humans) or corticosterone (in rodents) from the adrenal glands.
The binding process itself is highly specific and involves intricate molecular interactions between CRH and CRHR1. CRH binds to the extracellular domain of CRHR1, a G protein-coupled receptor (GPCR) located on the surface of cells in the anterior pituitary gland.
CRH binding induces a conformational change in CRHR1, triggering the activation of intracellular signaling pathways. This activation involves the coupling of CRHR1 to heterotrimeric G proteins, specifically Gαs, which in turn stimulates the enzyme adenylyl cyclase. Adenylyl cyclase catalyzes the conversion of ATP to cyclic AMP (cAMP), a second messenger molecule.
Increased cAMP levels activate protein kinase A (PKA), leading to the phosphorylation of downstream target proteins. These phosphorylation events ultimately result in the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland.
ACTH then travels through the bloodstream to the adrenal glands, where it binds to its receptor, the melanocortin 2 receptor (MC2R), triggering the synthesis and release of cortisol (or corticosterone).
In summary, CRH binding to CRHR1 initiates a complex molecular signaling cascade that culminates in the release of cortisol (or corticosterone), ultimately mediating the body's response to stress.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Corticotropin-releasing factor receptor 1 | A corticotropin-releasing factor receptor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P34998] | Homo sapiens (human) |
| Corticotropin-releasing factor-binding protein | A corticotropin-releasing factor-binding protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:P24387] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| hypericin | |||
| nbi 27914 | dialkylarylamine; tertiary amino compound | ||
| antalarmin | antalarmin : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidin-4-amine which is substituted by methyl groups at positions 2, 5, and 6, by a mesityl group at position 7, and in which the amino substituent at position 4 has been substituted by ethyl and butyl groups. It is an antagonist of corticotropin-releasing factor 1 (CRF-1) receptors (Ki = 1 nM). | pyrrolopyrimidine; tertiary amino compound | corticotropin-releasing factor receptor antagonist |
| ssr 125543a | SSR125543: a CRF1 receptor antagonist with antidepressant-like effects | amine | |
| cp 154526 | |||
| ucb 35625 | UCB 35625: J-113863 is the (trans)-isomer; structure in first source | ||
| r 121919 | |||
| pexacerfont | pyrazolopyridine | ||
| 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine | 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine: an hCRF(1) antagonist; structure in first source | ||
| nbi-34041 | NBI-34041: high-affinity CRF1 (corticotropin-releasing factor receptor 1) receptor antagonist for attenuating elevated stress response | ||
| dmp 696 | DMP 696: a CRF(1) receptor antagonist; structure in first source | ||
| cp 154526 | CP 154526: structure in first source | ||
| gsk 561679 | NBI 77860: a CRF1 receptor antagonist; structure in first source | ||
| bms 665053 | BMS 665053: structure in first source | ||
| nitd 609 | NITD 609: an antimalarial and coccidiostat; structure in first source |