Oxytocin hormone

Hormones are chemical messengers naturally produced in the human body by specialised cells that form endocrine glands. Endocrine glands do not have ducts and their products (that is, hormones) are directly secreted into the blood. In order to maintain proper communication for coordinated action in the body, hormones relay messages—either between two endocrine glands or between an endocrine gland and the target organ. This is known as the endocrine system.

Hormones that relay messages between two endocrine glands influence the release (by stimulation or inhibition) of all other hormones. These are secreted by the pituitary gland.

Let’s take a small detour here to know what is the pituitary gland: it is a small pea-sized gland located at the base of the brain. It is also called the “master gland”. The pituitary gland has two lobes—anterior and posterior.

• The anterior pituitary produces hormones of its own (upon action by hormones produced by the hypothalamus of the brain)
• The posterior lobe only stores and secretes two hormones synthesised by the hypothalamus—vasopressin and oxytocin.

Now, oxytocin, along with vasopressin (antidiuretic hormone), is one of two nanopeptide posterior pituitary hormones. It is synthesised in the hypothalamus of both males and females but has a more observable action in the latter. Its secretion is triggered in both sexes by romantic, physical and sexual intimacy and is therefore also dubbed the “love hormone”. In addition, it is produced in females during childbirth where it enhances uterine contractions and while breastfeeding where it lets down milk. Although more prominent in the female reproductive system, oxytocin has an important role in the male system as well. Oxytocin is thought to play part in male ejaculation, movement of sperm, production of testosterone as well as prostatic health. Oxytocin is also found to have some control over human behaviour and social interaction through its anxiolytic action (reduces anxiety).

The OXT gene encodes the oxytocin precursor protein in the hypothalamus. This precursor is stored as granules, after binding with specific binding proteins called neurophysins, in the posterior pituitary gland. With the appropriate stimulus, these granules dissolve, by the cleaving action of enzymes, and active oxytocin is released into the bloodstream.

Appropriate stimuli for oxytocin release include:

• Positive social stimuli
• Romantic intimacy 
• Hugging 
• Kissing 
• Cuddling 
• Sex
• Childbirth 
• Breastfeeding 

Positive feedback mechanism

Once the pituitary gland starts releasing oxytocin, continued secretion is maintained by a positive feedback mechanism. For example, when a baby suckles at the mother’s breast, the tactile stimulation of nerves in the nipple carries a message to the hypothalamus and oxytocin is released from the posterior pituitary. Oxytocin causes the breast milk to be let down, which in turn allows the baby to suckle more causing even more release of oxytocin in the same way. Therefore, the release of oxytocin progressively increases. This, however, is a self-limiting process; when the baby is satiated and stops feeding, the oxytocin release stops.

The hormone produces its effect by binding to specific oxytocin receptors which are expressed in various parts of the body. Its actions can be described as:

Physiological:

• Uterine contractions: Oxytocin receptors are present on the cells of the muscular myometrium of the uterus. Estrogen sensitises the uterus to the action of oxytocin and non-pregnant uterus is nearly completely resistant. Oxytocin released during labour increases the frequency and intensity of uterine contractions progressively by a positive feedback mechanism. When the uterine contractions are of sufficient duration, intensity and appear at frequent enough intervals, the delivery of the baby becomes possible. Sometimes, when uterine contractions are not strong enough or do not begin in time, synthetic analogues of oxytocin, like syntocinon, are administered intravenously to augment or induce contractions, respectively. 
• Milk ejection reflex or letting down breast milk: Tactile stimulation of the nerve endings in the nipple by the baby’s suckling mouth sends signals to the mother’s brain to initiate oxytocin and prolactin release. While prolactin regulates the synthesis of breast milk, oxytocin acts on the muscular myoepithelial cells in the breast, causing them to contract and squeeze stored milk out. With the availability of more milk, the baby sucks more. This starts a positive feedback loop that continually perpetuates oxytocin, and therefore the release of breast milk. Once the baby is sated, the suckling ceases. As does the oxytocin release. 
• Human sexual response: Increased levels of plasma oxytocin are associated both with sexual arousal and climax or orgasm in both sexes. The increased contractility and motility of the reproductive tract is partly responsible for the transportation of the egg and the sperm, respectively. 
• Negative effect on kidneys: Owing to the similar chemical structure as vasopressin, the antidiuretic hormone, oxytocin, too, at high doses can cause a decrease in urine output and increased sodium retention. This can result in swelling and pulmonary oedema. Therefore, when intravenous oxytocin is administered, it is done with close monitoring of fluid input and output. 
• Prostate gland: The prostate gland in males, dependent on testosterone, produces seminal fluid which is a major component of the sperm-carrying semen. Locally produced oxytocin in the gland is responsible for controlling the contractility of the prostate and synthesising testosterone within the gland for the seminal fluid creation and maintaining overall prostatic health. Oxytocin levels are altered in both benign and malignant diseases of the prostate indicating their role in them.

Psychological:

• Bonding: Oxytocin influences our capacity to form social bonds—it mediates the impact of early life nurturing on adult bond formation (how parents and children form a deep bond early on) and ability to maintain social bonds. While breastfeeding, the oxytocin released to let down breast milk also helps form a bond between mother and child. Oxytocin is also responsible for bonding between romantic partners.
• Anxiety and depression: The posterior pituitary hormones, oxytocin and vasopressin, play opposing roles in the regulation of anxiety, stress and sociality. While oxytocin has anxiolytic (anxiety-reducing) and antidepressant action, vasopressin induces both. Therefore shifting the oxytocin-vasopressin balance towards oxytocin through positive stimuli or medication can alleviate anxiety and depression. 
• Autism: This is a spectrum disorder. The autistic individual receives less reward from social stimuli than people who aren’t on the spectrum. Oxytocin is believed to play a role in social motivation. Studies have shown links between OXT gene mutations and autism.
• Drug addictions: Oxytocin is known to reduce tolerance to addictive drugs such as alcohol and opioids like heroin. It is also known to reduce withdrawal symptoms. By exerting an effect on the hypothalamus-pituitary-adrenal axis, it impacts adaptive processes like reward, stress response and memory. The hypothalamus, pituitary gland and adrenal glands (over the kidneys) are all responsible for releasing different hormones.

The properties of naturally occurring hormone oxytocin have been recreated in synthetic or analogous drugs that have proven useful. In present-day obstetrics, oxytocin analogues are irreplaceable. Oxytocin may be administered through intravenous or intramuscular injections, with intranasal sprays and sometimes even by patches placed in the gums. 

Oxytocin formulations used in medicine:

• Pitocin
• Syntocinon
• Carbetocin: a long-acting analogue of oxytocin designed to control postpartum haemorrhage by maintaining the tone of the uterus. 
• Desamino-oxytocin

Medical practitioners are divided on whether the use of oxytocin during childbirth is necessary and largely beneficial. Having said that, some of the uses that oxytocin is sometimes put to are: 

• Induce labour: In cases where labour does not set in naturally (post maturity or after 40 weeks of pregnancy are up) or when premature induction is necessary (as with prematurely ruptured membranes or water breaking, placental insufficiency, diabetic mother or erythroblastosis), oxytocin is administered as a slow intravenous infusion, typically at the dose of 5 IU in 500 mL of glucose or saline. The rate is increased gradually by gauging response on a partograph on which contractions are recorded pictorially. However, before starting oxytocin induction, some things should be ensured by the doctor:
  • Baby's position: Presentation of the baby is correct
  • Baby development: The baby’s lungs are adequately mature
  • No cephalopelvic disproportion: The doctor needs to check if the mother’s pelvis can accommodate the baby's head. In case the doctor feels the expecting mother's pelvis won't allow the passage of a large baby’s head, the oxytocin should not be given.
  • No placenta previa: Placenta previa is a condition in which the placenta partially or completely covers the expecting mother's cervix—the opening of the birth canal; haemorrhage can occur in such cases if they are not appropriately managed.
  • There’s no foetal distress: The baby’s heart rate during pregnancy should be between 110 to 160 beats per minute. A low foetal heart rate can indicate distress and is a cause for concern as without appropriate management, foetal death can occur. (Read more: Stillbirth) 
  • There are no previous uterine scars (from previous Caesarean delivery): increased contractility of the uterus post induction can cause the scar to rupture
• Augmentation of labour: In some cases, after labour contractions have set in, they may not progress adequately due to uterine inertia and the labour may become unduly prolonged. Only in such cases, after fulfilling the criteria mentioned above, oxytocin infusion can be started to increase the strength of uterine contractions in a gradual controlled manner. Oxytocin is preferred over prostaglandins and ergometrine drugs for this purpose as its dose can be controlled better, it allows intermittent relaxation of the uterus permitting better oxygen supply to the baby and does not cause the lower uterine segment to contract and restrict baby’s descent. 
• Prevention of postpartum haemorrhage: An oxytocin injection given immediately after childbirth can help to control post-delivery bleeding. It does this by causing contraction of the uterine muscle, especially around the blood vessels. Therefore, oxytocin effectively prevents haemorrhage due to the uterus losing its tone and becoming floppy after the delivery of the baby. 
• Lower segment Caesarean section: Owing to the same mechanism, bleeding after operative delivery of the baby is also possible and therefore oxytocin is administered. 
• Clearing the uterus after a miscarriage: After an incomplete abortion or miscarriage, some products of conception may remain retained inside the uterus. These products can easily become host to bacteria and can lead to catastrophic widespread infection. In order to completely clear the uterus of these contents, oxytocin can be useful. By inducing uterine contractions it aids in the expulsion of the conceptus. 
• Ease breast engorgement: At times the breast milk may not be let down adequately and the milk pools within the ducts of the breast tissue causing them to become painfully swollen—this is known as breast engorgement. Intranasal oxytocin (that is, oxytocin given through the nose) can be given a few minutes before putting the baby to the breast to increase milk ejection. This, however, does not increase the production of breast milk.

Adverse effects with oxytocin are generally dose related. Common side effects include:

• Cardiovascular effects: Headaches, slowing or fastening of heartbeat, fall in blood pressure and flushing.
• Vomiting: Some patients may experience nausea and vomiting  
• Water intoxication: At high doses, oxytocin has activity similar to the antidiuretic hormone and can reduce urine output while increasing sodium retention. This results in swelling, puffiness and sometimes even pulmonary oedema. 
• Uterine rupture: If the progressive increase in intensity, frequency and duration of uterine contractions go unchecked, violent uterine contractions can ultimately result in its rupture. 
• Effects in newborns: Jaundice in newborn could be a side effect of oxytocin given during labour.
• Birth asphyxiation and intrauterine death: Excessively strong and uncontrolled uterine contractions can restrict the baby’s respiration, and if prolonged, this can even cause death.