Oxytocin

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Oxytocin
Oxytocin
Structural formula without stereochemistry ( blue : three-letter code of the amino acids)
Properties of human protein
Mass / length primary structure 9 amino acids, 1007.19 g · mol -1
Precursor Oxytocin-Neurophysin-1 (106 amino acids)
Identifier
Gene names OXT  ; OT
External IDs
Drug information
ATC code H01 BB02
DrugBank DB00107
Drug class hormone
Occurrence
Homology family Oxytocin
Parent taxon Vertebrates

Oxytocin (also Ocytocin , from ancient Greek ὠκύς ōkys , German 'fast' , and ancient Greek τόκος tokos , German 'birth' : okytokos "easily giving birth"; in German sometimes also written Oxitozin ) is a hormone produced in the brain , which has an important meaning among including the birth process takes, which brings the uterus to to contract and thus triggers labor. Oxytocin also stimulates the mammary glands to release milk. At the same time, it not only influences the behavior between mother and child and between sexual partners , but also social interactions in general .

Oxytocin is a neuropeptide belonging to the group of proteohormones . It is formed in the paraventricular nucleus and to a lesser extent in the supraoptic nucleus (both core areas in the hypothalamus ). From here, oxytocin is transported via axons to the posterior lobe (neurohypophysis) of the pituitary gland, stored temporarily and released when required.

Henry Dale discovered oxytocin in the pituitary gland in 1906. He first described the effects of oxytocin in connection with the onset of labor and the speed of labor. Shortly thereafter, he came to research that suggested the connection between oxytocin and the secretion of breast milk during breastfeeding. Oxytocin was first isolated and synthesized together with vasopressin in 1953 by Vincent du Vigneaud , for which he received the Nobel Prize in Chemistry in 1955 . Today it is known that oxytocin acts as both a hormone and a neurotransmitter . The range of its effects is therefore greater than originally assumed.

structure

The primary structure of the human peptide oxytocin consists of nine amino acids with the sequence CYIQNCPLG. The two cysteine ​​residues form a disulfide bridge . The structure of oxytocin is very similar to vasopressin , also a nonapeptide (CYFQNCPRG) with a disulfide bridge, the sequence of which differs in two amino acids. The C-terminal glycine is in its amidated form.

physiology

Oxytocin is created from the precursor protein oxytocin-neurophysin (106 amino acids) by separating peptide bonds using proprotein convertase 1 , whereby a tripeptide is formed in addition to oxytocin and neurophysin (94 amino acids) . Oxytocin as well as vasopressin, angiotensin III and several enkephalins are broken down by the enzyme leucyl-cystinyl aminopeptidase .

The release of oxytocin is caused by every kind of pleasant skin contact. When breastfeeding through the suckling impulse of the baby, further through warmth and massage. The activity of neural networks in the brain, v. a. of the brain stem stimulates this release. The processes in the brain stem have the task of controlling fear and flight behavior . Here is z. B. the amygdala , but also other groups of neurons in the brain stem that control the cardiovascular system. Oxytocin thus plays an important role in regulating stress .

The oxytocin level is increased under the influence of MDMA , which explains the increased perception of positive emotions in other people in the MDMA intoxication.

Oxytocin is a positive allosteric modulator of μ- opioid receptors (MOR), i.e. it enhances the effect of orthosteric MOR agonists. Their efficiency ( E max ) is increased, not their affinity.

Oxytocin receptors

Oxytocin receptors (OXTR) are found in various types of body tissue , including the myoepithelial cells of the mammary glands , the tissues of the genital organs , the kidneys , the heart , the thymus , the pancreas and in fat cells . Only one OXTR isoform is known, but since the receptor is G-protein- coupled, cellular effects can be very different. In the prefrontal cortex, for example, the administration of oxytocin leads to spontaneous, rhythmic action potentials in interneurons .

Physiological effects

Oxytocin causes the muscles of the uterus ( myometrium ) to contract and thus triggers labor during delivery. It is used in clinical obstetrics as a drug in tablet form, as a nasal spray or intravenously (so-called " contractions "). Oxytocin also triggers after-pains - contractions of the uterine muscles, which serve to stop bleeding immediately after birth and later to involution of the uterus. This also leads to its use, in particular as an emergency medicinal product in the event of postnatal (postpartum) bleeding.

It also causes milk ejection (evacuation of the glandular vesicles) by stimulating the so-called myoepithelial cells of the mammary gland .

Oxytocin lowers blood pressure and cortisol levels , has a sedative and analgesic effect ( analgesic ) and can lead to improved wound healing . Research suggests that oxytocin reduces the effects of stress by acting on the so-called HPA axis ( hypothalamic-pituitary-adrenocortical axis ) .

Studies in animal models and in humans show that oxytocin has an effect on body weight. Repeated central injections of oxytocin into the brains of rats that were given a high-fat diet resulted in less weight gain than in rats injected with saline, given the same diet. This effect is based on an increased fat metabolism through increased beta-oxidation of free fatty acids. In a study in people with obesity , treatment with nasal spray containing oxytocin resulted in weight loss and improved cholesterol levels.

Due to its largely homologous structure to adiuretin , oxytocin can have its effect in high doses.

There is evidence that oxytocin has a regulating effect on the growth of neoplastic cells.

Behavior control

In addition to these physiological effects, oxytocin also influences behavior .

In animals

In the dairy cow , the oxytocin stored in its pituitary gland must be released in order to empty the udder by suckling the calf or by other stimuli to which the cow is conditioned . The oxytocin causes the milk to be injected into the milk cistern of the udder for five to eight minutes, from where it can be sucked off by the milking machine or pressed out by hand through the fingers during milking.

Studies of monogamous prairie voles ( Microtus ochrogaster ) suggest that oxytocin also plays a role in pair bonding. In contrast to polygamous mountain voles, prairie voles show a pronounced, long-term partner bond in pairs. Various studies have found a critical role for oxytocin in the development of this partner preference: If prairie voles were injected with an oxytocin antagonist, they behaved in a partner-like manner to polygamous mountain voles and no longer showed any longer-term social ties. The investigations showed that oxytocin is necessary and sufficient to express partner preference.

Interestingly, however, it does not seem to be the amount of endogenously released oxytocin per se that influences social bonding behavior, but the specific formation of oxytocin receptors in the brain. The receptor distributions in the brain of prairie and mountain voles differ in characteristic ways. In addition, prairie voles show similar receptor distributions as another monogamous species (meadow voles). Female mountain voles, which only show a long-term bonding behavior to their offspring in the period immediately after the birth of their offspring, show a change in their oxytocin receptor distribution exactly during this time.

A study published in 2016 also showed that prairie voles that had been exposed to aversive stimuli in experiments were then groomed particularly intensively by members of their own species who had been known to them for a long time ; this behavior was also attributed to the hormone oxytocin.

In humans

Perinatal period

Oxytocin plays an essential role perinatally ; an increase in the density of oxytocin receptors in the tissues of the uterus can be observed shortly before labor begins .

Breastfeeding and bonding

The milk ejection reflex of a nursing mother is controlled by the concentration of oxytocin. Oxytocin is released as soon as she hears the baby screaming or is thinking about breastfeeding . The neuropeptide not only increases the flow of milk when the baby is suckling, but also - together with the decrease in the stress hormone cortisol  - influences the mother's mood: “It creates pleasant, sometimes even pleasurable feelings. (...) This emotional effect creates one thing above all: It strengthens the emotional bond between the mother and the child. "

Babies produce oxytocin after they suckle.

Love and trust

In neurochemical research, oxytocin is associated with psychological states such as love , trust and calm in humans . These assumptions are based on experiments such as those carried out by Michael Kosfeld at the University of Zurich. Kosfeld had test subjects play an investor game with real money winnings, with some of the test persons generating an increased oxytocin level through a nasal spray. It was found that the people with an increased oxytocin level showed more confidence in their play partners. Beate Ditzen's working group researched the influence of oxytocin by asking spouses to discuss a topic that they often argue about. The results of the study suggest a calming and de-escalating effect of the neuropeptide.

aggression

The group of Carsten KW De Dreu brought oxytocin in humans but also with defensive aggression against outsiders , an action orientation in favor of the ingroup (ger .: in-group favoritism ) and a change of alliance behavior in context. Oxytocin stirs up prejudice, xenophobia and violence between members of different groups, the team at the University of Amsterdam concluded. The Freiburg psychologist Markus Heinrichs, a pioneer of oxytocin research on humans, rejects this: Preferring one's own people should not be equated with aggression towards others.

Increase in pleasure

The sexually stimulating effect of oxytocin has been repeatedly described in animals, but a lust-increasing effect has also been demonstrated in humans for both men and women. The high doses of oxytocin released during orgasm then cause a phase of relaxation and fatigue. “In any case, it is probably involved in the feeling of close personal connection after a satisfying sexual encounter, just as it strengthens the bond between the breastfeeding mother and her infant.” In addition, “the moderate exercise of tactile irritation on the skin organ at rhythmic intervals In other words: the caress "releases oxytocin" and leads to calming and a feeling of wellbeing that strengthens the bond between the people involved. "Oxytocin is released during pleasant physical contact such as hugs, caresses and massages , as well as when singing . Research suggests that the release of oxytocin can be triggered by pleasant sensory perceptions such as touch and warmth, by ingesting food, by stimulating smell, sound and light as well as by purely psychological mechanisms, especially as a result of appropriate conditioning ; it is also released in the brain during stress.

The research has led to oxytocin being occasionally discussed in public as an orgasm hormone , cuddle hormone, or loyalty hormone . In fact, the significance of oxytocin for feeling and acting has been confirmed in numerous studies; However, it should be noted that psychological states such as "love" do not correspond to any uniform biological phenomena.

The various triggers for an oxytocin release are used as possible explanations for the effectiveness of alternative healing methods such as hypnotherapy and meditation .

Oxytocin is also the subject of research in psychology in the study of social phobias and related disorders. Oxytocin increases envy and glee as well as aggressive behavior.

According to the latest results, the hormone could also work against Alzheimer's , schizophrenia and autism and create more confidence in patients . In children with autism, at least an increased activity was found in the brain region, which is responsible for processing social information.

Trade names

Oxytocin is commercially available in Germany, Austria and Switzerland under the name Syntocinon . In Germany it is available as a generic in various strengths (3 IU, 5 IU, 10 IU) . The preparation is approved for use before birth (usually for induction of labor) as well as for use after birth, especially in the case of peripartal bleeding. Oxytocin is therefore an indispensable emergency drug in the delivery room . At the beginning of 2019, a severe delivery bottleneck posed major problems for healthcare facilities across Germany.

Before August 7, 2008, an oxytocin preparation was also available in Germany as a nasal spray under the name Syntocinon. This was registered before the Medicines Act of 1978 came into force. A reauthorisation application from the manufacturer was not granted due to a lack of proven drug safety testing and a lack of justification for therapeutic effectiveness.

literature

  • 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. 177 f., 383 and passim.
  • K. Uvnäs-Moberg, I. Arn, D. Magnusson: The psychobiology of emotion: the role of the oxytocinergic system. In: Int J Behav Med. 12, 2005, pp. 59-65. PMID 15901214 .
  • Michael Kosfeld, Markus Heinrichs, Paul J. Zak, Urs Fischbacher, Ernst Fehr: Oxytocin increases Trust in Humans. In: Nature . 435, 2005, pp. 673-676. (PDF; 510 kB) ( Memento from April 17, 2012 in the Internet Archive )
  • Antonio Damasio : Brain trust. In: Nature. 435, 2005, p. 571.
  • Stefanie Kara: Oxytocin: Our miracle drug . In: The time . April 14, 2016. (Oxytocin is the pop star of the body's own substances: the hormone that makes us trust).
  • Kerstin Uvnäs Moberg: Oxytocin, the hormone close by: health - wellbeing - relationship. translated by Martina Wiese Springer Spektrum, Berlin 2016, ISBN 978-3-662-47358-0 .

College work

  • Katharina Lüdemann: Relationship between empathy and serum oxytocin concentration in 14-year-old adolescents. Medical Faculty Charité - Universitätsmedizin Berlin 2016, DNB 1100388028 , Dissertation Charité, Universitätsmedizin Berlin June 5, 2016, ( full text, PDF, 1.47 MB ).
  • Laura Katharina Mühlhausen: Investigation of the effect of sociodemographic factors and oxytocin receptor polymorphisms on the ability to empathize. Medical Faculty Charité - Universitätsmedizin Berlin 2016, DNB 1113012412 , Dissertation Charité, Universitätsmedizin Berlin 2016, (full text, PDF, 9.1 MB)

Web links

Wiktionary: Oxytocin  - explanations of meanings, word origins, synonyms, translations

Individual evidence

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  2. ^ Information from the Nobel Foundation on the 1955 award ceremony for Vincent du Vigneaud (English) .
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  33. ↑ The dark side of the cuddle hormone oxytocin.
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