Thyreoliberin

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Thyreoliberin
Thyreoliberin
Structural formula of thyreoliberin
Properties of human protein
Mass / length primary structure 3 amino acids
Precursor Prothyroliberin , 218 amino acids
Identifier
Gene name TRH
External IDs
Occurrence
Homology family Prothyroliberin
Parent taxon Euteleostomi

Thyrotropin-releasing hormone , and thyrotropin releasing hormone ( TRH ; thyrotropin -releasing hormone ) or protirelin , is a peptide hormone , the hormone release as in the hypothalamus is formed.

structure

Thyreoliberine, chemically L - pyroglutamyl - L -histidyl- L -prolinamide, is a modified tripeptide with the primary structure : (pyro-) Glu – His – Pro-NH 2 . Modifications to the amino and carboxy-terminal amino acids protect it from degradation by peptidases . It will be (218 amino acids) from the pro-thyrotropin-releasing hormone processed by the tetrapeptide Gln-His-Pro-Gly is cut out initially, which is then terminally amidated C-and N-terminal is cyclized.

The structure of thyreoliberin was first elucidated in 1969 by the research groups led by Roger Guillemin and Andrew Schally .

physiology

Under the influence of serotoninergic and adrenergic neurons, thyreoliberin biosynthesis in the hypothalamus is stimulated and its release is induced. In contrast to other releasing hormones , thyreoliberin only appears to be under the feedback control of the regulated hormones (T 3 and T 4 ) to a small extent . TRH is transported to the anterior lobe of the pituitary gland ( adenohypophysis ) via the hypothalamic-pituitary portal vein system. In the anterior lobe, thyroliberin stimulates the formation and release of prolactin and thyrotropin (TSH) , the so-called thyroid (thyroid) stimulating hormone. Via TSH, thyreoliberin also stimulates the secretion of the thyroid hormones T 4 and T 3 in the thyroid gland .

The TRH release is u. a. stimulates when the body temperature drops: The subsequent release of TSH and subsequent T4 stimulates the metabolism, which increases the body temperature via an increased sugar metabolism. Other energy-demanding mechanisms also stimulate TRH release.

As a stimulator of TSH and prolactin release, TRH is a neuropeptide hormone . On the other hand, it also acts as a neurotransmitter in regions of the brain outside the hypothalamus, as well as in the pancreas and thyroid.

Under the influence of the suprachiasmatic nucleus , the TRH release occurs in a circadian rhythm with maximum release around midnight and minimum release in the late afternoon. Ultradian secretion peaks were also observed at intervals of 2 to 4 hours. The rhythmic TRH release is also influenced by the limbic system, the pineal gland and other brain regions, which are important for the stress response.

If there is a defect in the anterior lobe of the pituitary gland (anterior pituitary insufficiency) so that the anterior lobe of the pituitary gland no longer or only reacts to a reduced extent to the thyroid liberin, the anterior lobe of the pituitary gland releases too little or no TSH despite an adequate supply of thyroid liberin leads to a reduced production and distribution of T 4 and T 3 . So-called secondary hypothyroidism develops .

If the supply of thyroliberine to the anterior lobe is disturbed, this has the same consequences as the reduced reactivity of the anterior pituitary gland just described; However, this is called tertiary hypothyroidism due to the different nature of its development mechanism . It arises z. B. with an interruption of the portal vascular system between the hypothalamus and pituitary gland ( Pickardt syndrome ).

In addition to its main action on the pituitary gland, Thyreoliberin also stimulates the release of prolactin , a hormone that stimulates milk production in the female breast.

In about half of the cases of patients with acromegaly or giant stature, after administration of TRH there is an increase in growth hormone secretion. This is not observed in healthy individuals.

The half-life is around two minutes. The cleavage is carried out by the metallopeptidase thyroliberinase (TRH degrading ectoenzyme).

Central nervous effects

A larger part of the thyroid liberin has a direct effect in the brain that has nothing to do with the effect in the thyroid regulating circuit. This also explains the slight retarding effect of an increased blood level of T 3 and T 4 on the TRH level.

Thyreoliberine is a neurotransmitter in the brain

  • on thermoregulation,
  • the pain suppression,
  • in the sleep-wake regulation,
  • slowing down food and fluid intake and
  • involved in a large number of other control processes.

Thyreoliberin also has indirect vegetative effects:

  • It stimulates gastric acid production and gastrointestinal peristalsis via the vagus nerve.
  • It stimulates insulin secretion via the sympathetic nervous system.
  • It also stimulates the pancreas in its exocrine function.
  • It increases heart rate and blood pressure.

Thyreoliberin test (TRH test)

The thyreoliberin test is a functional examination to check the thyroid control loop and the stimulability of the pituitary gland.

indication

  • Suspected anterior pituitary insufficiency
  • Suspected subclinical hypothyroidism or hyperthyroidism
    • The TRH test is rarely carried out with this question

Contraindications

  • Unstable angina pectoris
  • Recent myocardial infarction
  • Known epilepsy
  • Severe bronchial asthma
  • pregnancy

execution

  • The test is usually carried out on the patient lying down in the morning after breakfast.
  • A venous access is placed.
  • Then blood is first taken to determine the basal concentration of TSH in the serum.
  • Then 200 µg of thyreoliberine are slowly injected intravenously.
  • Half an hour later, another blood sample is taken to determine the stimulated concentration of TSH in the serum.
  • The laboratory takes serum from both blood samples and determines the concentration of TSH from both.

For fearful people, Thyreoliberin can also be given as a nasal spray.

rating

After administration of thyreoliberin, the TSH value must increase in healthy individuals by at least 2.5 times, up to a maximum of approx.

  • An increase in TSH to 2 to 20 mIU / l is normal.
  • In primary hyperthyroidism, there is an insufficient increase in thyrotropin (TSH).
    • Increase <2.5 mIU / l
  • In primary hypothyroidism there is an excessive increase in thyrotropin (TSH).
    • Increase> 20 mIU / l
  • With secondary hypothyroidism (pituitary defect), the TSH rise does not occur.
    • Increase <2.5 mIU / l

Side effects of the test

In general, the administration of TRH is well tolerated. Temporary abnormal sensations such as B. a feeling of warmth, taste sensations, dry mouth, hunger, dizziness and nausea or a fast heartbeat and urge to urinate. In rare cases, an increase in blood pressure, an angina pectoris attack or an asthma attack may occur. Therefore, the indication should be reconsidered in the case of corresponding previous illnesses.

Name of the preparation Protirelin

  • Antepan
  • Relefact
  • Thyroliberine
  • TRH Ferring

See also

swell

  1. ↑ Löffler / Petridas: Biochemistry and Pathobiochemistry . 9th edition. Springer-Verlag, Berlin 2014, ISBN 978-3-642-17972-3 , pp. 512, 513 .
  2. ^ A b c Hans-Christian Pape, Armin Kurtz, Stefan Silbernagl: Physiology . 7th edition. Georg Thieme Verlag, Stuttgart 2014, ISBN 978-3-13-796007-2 , p. 619 .
  3. ↑ UniProt P20396
  4. ↑ J. Boler et al .: The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide. In: Biochem. Biophys. Res. Commun. Vol. 37, 1969, pp. 705-710. PMID 4982117
  5. ↑ Kleine and Rossmanith, Hormone and Hormonsystem, 2010, Springer-Verlag Heidelberg.
  6. ↑ Löffler / Petridas: Biochemistry and Pathobiochemistry . 9th edition. Springer-Verlag, Berlin 2014, ISBN 978-3-642-17972-3 , pp. 513 .

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