Oxytocin: A Surprisingly Versatile Hormone

When I began my career in the pharmaceutical industry with Parke Davis, one surprise was the small amount of data required to achieve approval for a New Drug Application (NDA) prior to the 1962 Kefauver Harris Amendments. In 1938, for example, the NDA for Pitocin (oxytocin injection) contained fewer than 100 pages. At that time, there was no need to include proof of efficacy, a requirement that subsequently added countless volumes of documents to all submissions.

Oxytocin was designated an "old drug," a term used for drugs on the market before passage of the 1962 amendments. The indications listed in the NDA were limited to inducing labor or strengthening contractions during childbirth and controlling bleeding. Current indications are still related to use in initiating and improving uterine contractions, although much more has been learned about this remarkably versatile and surprising hormone.

New studies have shown that oxytocin can affect maternal behavior, social bonding and even sexual pleasure. Moreover, oxytocin can make us more sympathetic, supportive and open with our feelings, such that its influence extends into romantic relationships. Books have been written extolling the properties of oxytocin, calling it the hormone of calm, love, trust, passion and intimacy.^1,2,3,4  It, along with dopamine, endorphin and serotonin, has been described as one of the happy chemicals. Studies have been conducted to determine whether oxytocin can be used to correct some of the interpersonal deficiencies brought on by autism. It is even being tested as an anti-anxiety drug. One website gives 10 reasons why oxytocin is the most amazing molecule in the world, perhaps not an exaggeration.⁵ This article briefly describes this versatile hormone and how other uses have been discovered since its approval.

Oxytocin

"Oxytocin," derived from the Greek oxys and tokos, meaning quick birth, was named after its uterine-contracting properties were discovered by British pharmacologist Sir Henry Hallett Dale in 1906. The sequence of nine amino acids in its structure was elucidated by Vincent du Vigneaud, Charlotte Ressler and Stuart Trippett in 1953, and synthesized biochemically by duVigneaud that same year.⁶ Du Vigneaud was awarded the Nobel Prize in Chemistry in 1955 for his achievement.

Oxytocin is a very abundant neuropeptide exerting a wide spectrum of central and peripheral effects as a neurohormone, neurotransmitter or neuromodulator. It is produced mainly in the hypothalamus, where it is either released into the blood via the posterior lobe of the pituitary gland or to other parts of the brain and spinal cord, where it binds to oxytocin receptors to influence behavior and physiology. The receptors are described as G-protein-coupled receptors, which require Mg⁺² and cholesterol to function. The behavioral effects 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 brain stem.⁷ Peripheral actions mainly reflect secretion from the pituitary gland and are responsible for the stimulatory effects on the mammary glands (the hormone activates contractions of muscular cells around the milk glands) and the uterus. Moreover, it has been discovered that oxytocin also is released in the pituitary of the fetus, which contributes to additional contraction of the mother's uterus.⁸

Potential Uses

The excitement over oxytocin began in the 1990s when researchers discovered that breastfeeding women are calmer in the face of exercise and psychosocial stress than bottle-feeding mothers. More recent literature has shown a number of other uses. Oxytocin levels are high under stressful conditions, such as social isolation and unhappy relationships.⁹

New investigations show that oxytocin can make us more sympathetic, supportive and open with our feelings. These findings have led some researchers to investigate whether oxytocin can be used in couple's therapy. Oxytocin levels increase during periods of falling in love and also correlated with the longevity of a relationship.¹⁰ A recent study was the first to assess whether people with variations in the their oxytocin receptor gene have a harder time maintaining romantic relationships than those who do not. The researchers found that women with a specific variation were not as close to their partners as women without it. These women were more likely to report having had a marital crisis. Although it is not known how this variation affects the oxytocin system, it may result from fewer oxytocin receptors in the brain. People with fewer receptors would be less sensitive to the hormone's effects.¹¹

Oxytocin appears to play a dual role in triggering or reducing anxiety, depending on the social context. A recent study has linked it to social stress and its ability to increase anxiety and fear in anticipation of future stress. Oxytocin appears to strengthen negative social memory and anxiety by triggering an important signaling molecule-ERK (extracellular signal regulated kinases)-that becomes activated for several hours after a negative social experience. Experiments with mice have established that oxytocin is essential for strengthening the memory of social interactions and that it increases fear and anxiety in stressful situations.¹¹

Oxytocin also may reduce reward-driven food intake in humans. Researchers have investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 minutes after the hormone was administered. Oxytocin attenuated basal and postprandial levels of cortisone and ACTH, and curbed meal-related rise in plasma glucose. By doing so, oxytocin markedly reduced snack consumption.¹²

Individuals with autism show an altered ability to recognize faces and brain activations to facial stimuli. In healthy adults, oxytocin promotes both and modulates brain activity. Magnetic resonance imaging has shown that a single intranasal dose of oxytocin increases amygdala activity in response to facial stimuli in autistic adults. This suggests that oxytocin might be used as a treatment modality. (Individuals with autism fail to recognize faces and to integrate facial expressions with emotions, which is caused by impaired social cognitive abilities.)

Final thoughts

Oxytocin has become increasingly important to neurobiologists, psychologists, psychiatrists, sociologists and economists prompted by the discovery of the plethora of behavioral functions it regulates. The discovery in recent years of multiple pro-social and anti-stress effects makes the application of oxytocin a promising target for psychotherapeutic intervention and treatment of numerous psychiatric illnesses. Long-term studies, however, will be required to ascertain whether the benefits of oxytocin treatments are sustainable.¹³

References

1. Moberg U. The Hormone of Closeness: The Role of Oxytocin in Relationships. London, England: Pinter & Martin Ltd; 2013.
2. Hertoghe T. Passion, Sex and Long Life, the Incredible Oxytocin Adventure. Amsterdam, The Netherlands: Hertoghe Pub.; 2010.
3. Zak PJ. The Moral Molecule: The Source of Love and Prosperity. New York, NY: Penguin Group; 2012.
4. Hoveskeland B. The Oxytocin Opera. Self-published; 2013.
5. Dvorsky G. Io9 website. http://io9.com/5925206/10-reasons-why-oxytocin-is-the-most-amazing-molecule-in-the-w...Posted 12 July 2012. Accessed 18 August 2013.
6. Oxytocin. Wikipedia. http://en.wikipedia.org/wiki/Oxytocin. Accessed 17 July 2013.
7. The Oxytocin Molecule. World of Molecules website. http://www.worldofmolecules.com/emotions/oxytocin.htm. Accessed 22 July 2013.
8. Nuland SB. The Wisdom of the Body. New York, NY: Alfred A Knopf; 1997.
9. Lukas ML, Neumann ID. Brain Oxytocin is a Main Regulator of Prosocial Behavior-Link to Psychopathology, Autism- A Neurodevelopmental Journey from Genes to Behaviour. Valsamma Eapen, ed. Rijeka, Croatia: InTech Europe; 2011.
10. Gravotta L. Be mine forever: oxytocin may help build long-lasting love. Scientific American.http://www.scientificamerican.com/article.cfm?id=be-mine-forever-oxytocin&print=true. 12 February 2013. Accessed 13 August 2013.
11. DeAngelis T. The two faces of oxytocin. American Psychological Association website. http://www.apa.org/monitor/feb08/oxytocin.aspx. February 2008. Accessed 12 July 2013.
12. Volker O. et al. Oxytocin reduces reward-driven food intake in humans. [Published online ahead of print 8 July 2013]. Diabetes. http://diabetes.diabetesjournals.org/content/early/2013/07/01/db13-0663.abstract. Accessed 30 July 2013.
13. Elsevier. A cautionary note on oxytocin as a treatment for psychiatric disorders. Science Daily. http://www.sciencedaily.com/releases/2013/08/130812102714.htm . Accessed 18 September 2013.