Target type: biologicalprocess
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a thyrotropin-releasing hormone (TRH) stimulus. TRH increases the secretion of thyroid-stimulating hormone by the anterior pituitary. [GO_REF:0000071, GOC:TermGenie, PMID:21382270]
Thyrotropin-releasing hormone (TRH), also known as thyrotropin-releasing factor (TRF), is a tripeptide hormone that plays a crucial role in the regulation of thyroid hormone production. Its primary function is to stimulate the release of thyroid-stimulating hormone (TSH) from the anterior pituitary gland. The cellular response to TRH involves a complex cascade of signaling events.
Upon binding to its specific G protein-coupled receptor (TRH receptor), TRH initiates a signaling pathway that ultimately leads to the release of TSH. This process involves the following steps:
1. **Binding of TRH to its receptor:** TRH binds to its receptor, located on the plasma membrane of thyrotrophs, the cells in the anterior pituitary that produce TSH.
2. **Activation of G protein:** TRH binding activates a G protein coupled to the receptor. This G protein is a heterotrimeric complex composed of alpha, beta, and gamma subunits. Upon activation, the alpha subunit dissociates from the beta and gamma subunits.
3. **Activation of phospholipase C (PLC):** The activated alpha subunit of the G protein binds to and activates phospholipase C (PLC), an enzyme that cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol trisphosphate (IP3) and diacylglycerol (DAG).
4. **Elevation of intracellular calcium:** IP3 diffuses into the cytoplasm and binds to IP3 receptors on the endoplasmic reticulum (ER), leading to the release of calcium ions (Ca2+) from the ER. The increased intracellular calcium concentration plays a crucial role in stimulating TSH release.
5. **Activation of protein kinase C (PKC):** DAG, the other second messenger produced by PLC, activates protein kinase C (PKC). PKC is a serine/threonine kinase that phosphorylates various proteins, including transcription factors and other signaling molecules, contributing to the regulation of TSH release.
6. **Activation of calcium-dependent kinases:** The increase in intracellular calcium concentration activates calcium-dependent kinases, such as calmodulin kinase II (CaMKII). CaMKII further phosphorylates proteins involved in TSH release, including components of the exocytotic machinery responsible for TSH vesicle fusion with the plasma membrane.
7. **Exocytosis of TSH:** The combined effects of calcium influx, activation of PKC and CaMKII, and other signaling events lead to the exocytosis of TSH vesicles from the thyrotrophs. TSH is then released into the bloodstream, where it travels to the thyroid gland and stimulates the synthesis and release of thyroid hormones (T3 and T4).
8. **Negative feedback regulation:** Once thyroid hormone levels in the bloodstream reach a certain threshold, they exert a negative feedback effect on the hypothalamus and pituitary gland. This feedback loop reduces the production and release of TRH and TSH, effectively regulating thyroid hormone levels within a narrow range.
The cellular response to TRH is a complex and tightly regulated process that involves multiple signaling pathways and molecular interactions. It is essential for maintaining appropriate thyroid hormone levels, which are crucial for regulating metabolism, growth, and development.'
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Protein | Definition | Taxonomy |
---|---|---|
Thyrotropin receptor | A thyrotropin receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:P16473] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
org 41841 | Org 41841: structure in first source | pyrimidines; thienopyrimidine | |
N-[4-[[5-[5-hydroxy-4-oxo-3-(phenylmethyl)-1,2-dihydroquinazolin-2-yl]-2-methoxyphenyl]methoxy]phenyl]acetamide | quinazolines |