TSH (Thyreoidea-stimulierendes Hormon): the pathway in the body

TSH (Thyreoidea-stimulierendes Hormon) is part of the pathway “Thyroid hormones”. This page shows the whole pathway; the station of TSH (Thyreoidea-stimulierendes Hormon) is highlighted.

Where this laboratory value sits: TSH — from the pituitary gland. In response, the pituitary gland produces TSH and releases it into the blood. TSH reaches the thyroid and stimulates every single step of hormone synthesis there. Source 1

In brief

The thyroid hormones T4 and T3 are iodine-containing derivatives of the amino acid tyrosine; their formation is controlled by the pituitary hormone TSH. In the cells, T4 is converted to T3, which changes the reading of certain genes in the nucleus.

The pathway step by step

1. TRH → TSH In response, the pituitary gland produces TSH and releases it into the blood. TSH reaches the thyroid and stimulates every single step of hormone synthesis there. Source 1
2. TSH → Iodide in the cell NIS · Sodium The transporter NIS brings iodide from the blood into the thyroid cell. It is driven by sodium flowing in at the same time. Source 2, 6
3. Iodide in the cell → Iodinated thyroglobulin TPO · Hydrogen peroxide, Haem iron At the edge of the follicle, thyroid peroxidase (TPO) attaches iodine to tyrosine units of the large protein thyroglobulin. For this it needs hydrogen peroxide, supplied by the enzyme DUOX2. Source 3, 6
4. Iodinated thyroglobulin → T4 and T3 TPO (coupling) The same TPO couples pairs of iodinated tyrosines, forming T4 and, in smaller amounts, T3. The cell retrieves the thyroglobulin, frees the hormones and releases them into the blood. Source 3, 1
5. Free T4 → Free T3 Deiodinase D1, D2 · Selenium Deiodinases remove a single iodine atom from the outer ring of T4. This yields T3, the form that acts at the receptor. The deiodinases carry selenium in their active centre. Source 4, 6
6. Free T4 → Reverse T3 Deiodinase D3 · Selenium The deiodinase D3 instead removes an iodine atom from the inner ring. The resulting reverse T3 does not fit the receptor and is broken down further. In this way the cell itself sets how much T3 it has. Source 4
7. Free T3 → T3 receptor In the nucleus, T3 binds to its receptor (TR). The receptor already sits on specific stretches of DNA, usually together with a second protein. Source 5
8. T3 receptor → Gene transcription With T3 bound, the receptor changes shape, releases repressing partner proteins and recruits activating ones. This switches transcription of the associated genes on or off. Source 5

Cofactors in this pathway

• Iodine — Building block of T4 and T3; the thyroid takes it up as iodide via NIS Source 2, 6In the ORY catalogue as a laboratory value: Jod (Urin)
• Selenium — As selenocysteine in the active centre of the deiodinases that convert T4 to T3 Source 4, 6In the ORY catalogue as a laboratory value: Selen
• Iron — As haem iron, cofactor of thyroid peroxidase, which attaches iodine to thyroglobulin Source 6In the ORY catalogue as a laboratory value: Eisen
• Tyrosine — Building block in thyroglobulin to which iodine is attached Source 3In the ORY catalogue as a laboratory value: Tyrosin
• Sodium — Drives the transporter NIS, which brings iodide into the thyroid cell Source 2In the ORY catalogue as a laboratory value: Natrium (intrazellulär)

What acts on this pathway

• Thiamazole — Thiamazole inhibits thyroid peroxidase, so less iodine is attached to thyroglobulin. The prescribing information describes exactly this mechanism. Source 7

Sources

1. Ortiga-Carvalho TM, Chiamolera MI et al. Hypothalamus-Pituitary-Thyroid Axis. Compr Physiol 2016 · PubMed 27347897
2. Portulano C, Paroder-Belenitsky M et al. The Na+/I- symporter (NIS): mechanism and medical impact. Endocr Rev 2014 · PubMed 24311738
3. Citterio CE, Targovnik HM et al. The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 2019 · PubMed 30886364
4. Bianco AC, Dumitrescu A et al. Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocr Rev 2019 · PubMed 31033998
5. Brent GA. Mechanisms of thyroid hormone action. J Clin Invest 2012 · PubMed 22945636
6. Köhrle J. Selenium, Iodine and Iron-Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism. Int J Mol Sci 2023 · PubMed 36834802
7. US prescribing information Thiamazole/Methimazole (DailyMed), section Clinical Pharmacology · Prescribing information

Whole pathway: Thyroid hormones

Related pathways

• Iodine — iodide in the cell
• Vitamin C — Selen, Eisen
• 8-OHdG — Selen, Eisen
• Borrelia — Selen, Eisen
• IgG antibodies to food — Selen, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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