A hormone (a peptide) present in the rear part of the pituitary gland (the neurohypophysis) of many vertebrates. In humans, it is produced in the hypothalamus, but stored in and released from the pituitary gland. In lactating females it is released when the newborn suckle, thereby promoting milk-ejection. It also induces contractions of the uterus during labour. Its role in males is unknown.
In the brain, oxytocin is involved in social recognition and bonding, and might be involved in the formation of trust between people.Synthesis, storage and release
Oxytocin is made in magnocellular neurosecretory cells in the supraoptic nucleus and paraventricular nucleus of the hypothalamus and is released into the blood from the posterior lobe of the pituitary gland. Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.
In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin as shown in the inset of the figure;
Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus.
Structure and relation to vasopressin
Oxytocin is a peptide of nine amino acids (a nonapeptide). The sequence is cysteine - tyrosine - isoleucine - glutamine - asparagine - cysteine - proline - leucine - glycine (CYIQNCPLG).
The structure of oxytocin is very similar to that of vasopressin (cysteine - tyrosine - phenylalanine - glutamine - asparagine - cysteine - proline - arginine - glycine), also a nonapeptide with a sulfur bridge whose sequence differs from oxytocin by 2 amino acids.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects.
Actions
Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. The actions of oxytocin are mediated by specific, high affinity oxytocin receptors. The oxytocin receptor is a G-protein-coupled receptor which requires Mg2+ and cholesterol.
Peripheral (hormonal) actions
The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. Oxytocin receptors are expressed by the myoepithelial cells of the mammary gland, and in both the myometrium and endometrium of the uterus at the end of pregnancy. In some mammals, oxytocin receptors are also found in the kidney and heart.
Letdown reflex – in lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be 'let down' into a collecting chamber, from where it can be extracted by sucking at the nipple. these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituary gland. Oxytocin release during breastfeeding causes mild but often painful uterine contractions during the first few weeks of lactation. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition is normal. (Takayanagi 2005) Oxytocin is secreted into the blood at orgasm – in both males and females (Carmichael et al 1987). More important, in several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and in humans, high doses of oxytocin can result in hyponatremia. Oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation. (Takayanagi 2005)Actions of oxytocin within the brain
Oxytocin secreted from the pituitary gland cannot re-enter the brain because of the blood-brain barrier. Instead, the behavioral effects of oxytocin are thought to reflect release from centrally-projecting oxytocin neurons, different from those that project to the pituitary gland. Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the amygdala, ventromedial hypothalamus, septum and brainstem. Oxytocin injected into the cerebrospinal fluid causes spontaneous erections in rats (Gimpl 2001), reflecting actions in the hypothalamus and spinal cord. In the Prairie Vole, oxytocin released into the brain of the female during sexual activity is important for forming a monogamous pair bond with her sexual partner. Oxytocin has a role in social behaviors in many species, and so it seems likely that it has similar roles in humans. Sheep and rat females given oxytocin antagonists after giving birth do not exhibit typical maternal behavior. By contrast, virgin sheep females show maternal behavior towards foreign lambs upon cerebrospinal fluid infusion of oxytocin, which they would not do otherwise. Oxytocin reduces blood pressure and cortisol levels, increasing tolerance to pain, and reducing anxiety. In a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Nasally-administered oxytocin has also been reported to reduce fear, possibly by inhibiting the amygdala (which is thought to be responsible for fear responses) (Kirsch 2005). According to some studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiates, cocaine, alcohol) and reduces withdrawal symptoms. (Gimpl 2001)
Uses
Synthetic oxytocin is sold as medication under the trade names Pitocin and Syntocinon and also as generic Oxytocin. Oxytocin given intravenously does not enter the brain in significant quantities - it is excluded from the brain by the blood-brain barrier.
Injected oxytocin analogues are used to induce labour and support labour in case of non-progression of parturition. Oxytocin is also used in veterinary medicine to facilitate birth and to increase milk production. The tocolytic agent atosiban (Tractocile®) acts as an antagonist of oxytocin receptors;
Some have suggested that the trust-inducing property of oxytocin might help those who suffer from social anxieties, while others have noted the potential for abuse with confidence tricks.
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