thyroid-stimulating hormone signaling pathway

Definition

Target type: biologicalprocess

A G protein-coupled receptor signaling pathway initiated by thyroid-stimulating hormone (thyrotropin) binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:gap, PMID:10809230]

The thyroid-stimulating hormone (TSH) signaling pathway is a crucial endocrine system cascade that regulates thyroid hormone production and metabolism. The pathway initiates when TSH, produced by the pituitary gland, binds to its receptor (TSHR) on the surface of thyroid follicular cells. This binding activates the TSHR, a G protein-coupled receptor (GPCR), triggering a series of intracellular signaling events.

The activated TSHR stimulates the release of Gαs protein, which in turn activates adenylyl cyclase. Adenylyl cyclase converts ATP into cyclic adenosine monophosphate (cAMP), a second messenger molecule. cAMP then activates protein kinase A (PKA), which phosphorylates and activates downstream target proteins involved in thyroid hormone synthesis and secretion.

One of the primary targets of PKA is the transcription factor thyroid transcription factor 1 (TTF-1), which regulates the expression of genes encoding thyroid hormone biosynthetic enzymes. These enzymes include thyroglobulin (Tg), thyroid peroxidase (TPO), and deiodinases. Tg is a large glycoprotein that serves as a scaffold for thyroid hormone synthesis, while TPO catalyzes the iodination of tyrosine residues in Tg, a crucial step in thyroid hormone production. Deiodinases are responsible for the conversion of inactive T4 (thyroxine) to active T3 (triiodothyronine).

PKA also activates other signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway, which contributes to the regulation of thyroid cell growth and differentiation.

The activation of the TSH signaling pathway results in the increased production and secretion of thyroid hormones T3 and T4. These hormones exert a wide range of physiological effects, including regulating metabolism, growth, development, and temperature regulation.

In summary, the TSH signaling pathway is a complex cascade of events that starts with TSH binding to its receptor and culminates in the production and secretion of thyroid hormones. This pathway plays a critical role in maintaining homeostasis by regulating thyroid hormone levels and ensuring proper thyroid function.'
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Proteins (1)

Compounds (2)