Somatropin

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Somatropin
Somatropin
Ribbon model of somatropin based on crystal structure.

Existing structural data : 1a22 , 1axi , 1bp3 , 1hgu , 1huw , 1hwg , 1hwh , 1kf9 , 3hhr

Properties of human protein
Mass / length primary structure 191 amino acids
Secondary to quaternary structure 1-, 2-, 3-, 4-, or 5-mer in homo- and heteropolymer combinations
Isoforms 4th
Identifier
Gene names GH1  ; GH-N, GHN, GH, hGH-N
External IDs
Drug information
ATC code H01 AC01
DrugBank DB00052
Occurrence
Homology family Somatropin
Parent taxon Vertebrates

Somatropin or somatotropin (also called somatotropic hormone ) is a proteohormone that occurs as a growth hormone in the human and animal organism and is formed in the brain in the anterior lobe of the pituitary gland .

Recombinantly produced somatropin (rhGH) is used as a medicinal substance in cases of growth hormone deficiency (GHD) due to insufficiency of the pituitary gland .

Synonyms

There are a number of synonyms and abbreviations for the somatropin:

  • Somatotropic hormone (STH)
  • Human Growth Hormone (HGH)
  • Growth Hormone (GH)
  • Growth hormone (WH)
  • Somatropin ( INN )

structure

The primary structure of human somatropin consists of 191 amino acids with a molecular mass of 22,125  Da . There are species-specific variants of the hormone. The tertiary structure consists of four α-helices with two intramolecular disulfide bonds .

Education and Regulation

Somatropin is produced in the α cells of the anterior pituitary gland . Its spurt-wise release is regulated by the hypothalamus with its somatropin-releasing factor (SRF, GHRH growth hormone-releasing hormone, GRF, somatoliberin) and somatostatin . Most somatropin is produced during sleep . The Puberty is the age with the ausgeprägtesten somatropin production.

A lack of an energy substrate ( hypoglycemia , fasting , physical activity), an increase in the serum level of certain amino acids (e.g. through a high-protein diet), fever and psychological stress are secretion stimuli for somatropin. Somatropin is negatively regulated by somatostatin , an inhibiting hormone ( Growth-Hormone-Inhibiting-Hormone, GHIH), which is produced in the pancreas and hypothalamus .

Somatropin is the most important hormone in the pituitary gland in quantitative terms . It makes up about ten percent by weight of the dried gland.

Normal values

Specifying a normal value for the concentration of somatropin would be wrong, since there is a daily rhythm and a life rhythm of secretion . There are also factors that stimulate acute secretion. That is why several values ​​are usually taken in a daily profile.

The somatropin suppression test has proven itself in the diagnosis of acromegaly and giant stature . Autonomous somatropin secretion is used when the somatropin level does not fall below 1.0 µg / l during oral glucose exposure (oGTT, 100 g glucose).

The individual determination of somatropin is unsuitable for the diagnosis of a somatropin deficiency because of the episodic (pulsatile) spontaneous secretion and the resulting phases with undetectable hormone levels. The determination under stimulation is possible with the following methods:

Limit values: 11.5 ng / ml for people of normal weight with a BMI ≤ 25 kg / m², 8 ng / ml for overweight people with a BMI between 25 and 30 kg / m² and 4.2 ng / ml for obese people with a BMI> 30 kg / m²
Limit values: severe deficiency at <3 ng / ml; partial deficiency at 3–7 ng / ml; normal at> 16 ng / ml

Effect, deficiency and overproduction

Somatropin is essential for normal growth. With a decreased production or a decreased response of the cells to somatropin, it comes to a short stature . Overproduction results in gigantic growth or acromegaly (excessive growth in the not yet ossified areas in the acres such as the nose, chin, fingers and cranial bones as well as in all soft tissues (e.g. cardiomegaly )).

In adulthood, a lack of somatropin leads to a variety of symptoms:

Also, a lack of somatropin leads to too

  • an increased cardiovascular risk profile,
  • decreased quality of life and
  • the increased use of medical services.

These symptoms are associated with a reduced life expectancy.

Somatropin works indirectly by attaching to the somatropin receptor , which is a transcription factor and increases the expression of the protein insulin-like growth factor-1 (IGF-1). This in turn binds to its receptor ( IGF1R ), which is also a transcription factor and controls the production of a large number of other proteins. If the somatropin receptor is changed by mutations , the cells do not respond or respond less to somatropin, which is referred to as somatropin resistance or Laron's syndrome .

More precisely, somatropin mainly affects the following organs:

  • Muscle, liver (via IGF-1)
  • Bone, kidney (via EGF )
  • Cartilage (via Ib FGF )

Anabolically, it acts primarily on muscles , liver and bones, in that it leads to increased absorption and utilization of amino acids. Somatropin increases the blood sugar level (through glycogenolysis ) and has a lipolytic effect on the fat cells, i.e. it breaks down fat.

In ruminants , somatropin ensures that lactation is maintained (see bovine somatropin ). A somatotropin deficiency leads to dwarfism in domestic dogs .

Use as a medicinal substance

Somatropin has been used to treat short stature since 1963 when it is caused by a lack of growth hormone. It was obtained from the pituitary glands of the dead until it was banned worldwide in early 1985 because it resulted in the transmission of AIDS and Creutzfeldt-Jakob disease in patients and subsequent deaths. Somatropin has been produced recombinantly since December 1985. Today, growth hormone is also used for the therapy of low body height if another underlying disease causes this short stature, for example in Ullrich-Turner syndrome , Prader-Willi syndrome , in chronic kidney failure or in short stature as a result of intrauterine growth retardation ( SGA, Small for Gestational Age). It has also been used for a number of years as a replacement therapy for severe growth hormone deficiency in adulthood.

In December 2011 the European Medicines Agency (EMA) confirmed the positive risk-benefit ratio for somatropin-containing medicines.

Non-medical use

Synthetic somatropin is used as an "anti-aging" agent and there is no evidence of long-term benefit. It is often misused due to its muscle-building properties in bodybuilding and other sports. For this purpose it is sometimes combined with testosterone , insulin , trenbolone and the thyroid hormone triiodothyronine (T3). In the meantime, however, dangerous total counterfeit drugs allegedly containing somatropin have emerged, which were intended for use in the bodybuilder scene. In the doping scene, somatropin is generally regarded as an expensive "miracle weapon".

The use of somatropin in people without an existing deficiency can lead to acromegaly with severe side effects, which are often irreversible .

Initial results from the Thymus Regeneration, Immunorestoration, and Insulin Mitigation study   raised ethical questions such as "Do we want a world where millions starve and others grow old?"

proof

Somatropin has been reliably detectable since 1999 using a method developed by the German hormone researcher Christian Strasburger . Another method was developed by Peter Sönksen in 2000.

Trade names

Monopreparations

Genotropin (D, A, CH), Humatrope (D, A, CH), Jintropin (RU, CN ), Norditropin (D, A, CH), NutropinAq (D, A), Omnitrope (D, A, CH), Saizen (D, A, CH), Zomacton (D, A)

Omnitrope ( Sandoz ) is the trade name for somatropin, which has been approved as a biosimilar since 2006 .

Web links

literature

  • Siegfried Zabransky, Michael B. Ranke: Growth hormone therapy in pediatrics. Palatium-Verlag, Mannheim 2002, ISBN 3-920671-46-5 .
  • Lois Jovanovic, Genell J. Subak-Sharpe: Hormones. The medical manual for women. (Original edition: Hormones. The Woman's Answerbook. Atheneum, New York 1987) From the American by Margaret Auer, Kabel, Hamburg 1989, ISBN 3-8225-0100-X , pp. 20, 48 ff. And 387.

Individual evidence

  1. PDB  1hgu
  2. Somatropin data sheet (PDF) at EDQM , accessed on June 6, 2011.
  3. UniProt P01241
  4. ^ William F. Ganong: Textbook of Medical Physiology: Human Physiology for Students of Medicine and Doctors . Springer, Berlin / Heidelberg 2013, ISBN 978-3-662-00627-6 , pp. 352 ( limited preview in Google Book search).
  5. G. Corneli, C. Di Somma, R. Baldelli, S. Rovere, V. Gasco, CG Croce, S. Grottoli, M. Maccario, A. Colao, G. Lombardi, E. Ghigo, F. Camanni, G. Aimaretti: The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. In: European Journal of Endocrinology. 2005, pp. 257-264.
  6. Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. In: Journal of Clinical Endocrinology & Metabolism. 1998, pp. 379-381.
  7. a b Anton Luger: Substitution therapy for growth hormone deficiency. In: Journal for Fertility and Reproduction. Edition for Austria. 17 (1), 2007, pp. 15-18.
  8. ^ Z. Laron: Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. In: The Journal of clinical endocrinology and metabolism . Volume 89, Number 3, March 2004, pp. 1031-1044. PMID 15001582 .
  9. ^ Z. Laron: Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity? In: Mechanisms of aging and development. Volume 126, Number 2, February 2005, pp. 305-307, doi: 10.1016 / j.mad.2004.08.022 . PMID 15621211 . (Review).
  10. ^ European Medicines Agency confirms positive benefit-risk balance of somatropin-containing medicines. EMA press release, December 15, 2011.
  11. Customs investigation warns of totally counterfeit medicine "SOMATROPE". ( Memento from January 1, 2011 in the Internet Archive )
  12. Plagiarism pills make biceps dwindle. In: Der Spiegel. 42/2009.
  13. "Can We Restore Thymus Function to Cheat Death?"
  14. "He who lives forever makes no room for others" Zeit Online from July 15, 2019
  15. ^ Evidence of doping with HGH ( memento of February 18, 2009 in the Internet Archive ).
  16. 10 years of biosimilars in Europe - an overview of biosimilar approvals . In: Pro Biosimilars . April 12, 2016 ( probiosimilars.de [accessed November 26, 2018]).