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Oxytocin has been best known for its roles in female reproduction. It is released in large amounts during labor, and after stimulation of the nipples. It is a facilitator for childbirth and breastfeeding. However, recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, bonding, and maternal behaviors. This small nine amino acid peptide is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug. The hormone of labor during the course of the last 100 years has had multiple orgasms to be the hormone of love. Many more shall be seen in the times to come!
Traditionally, it has been artists, poets, and playwrights who have made the greatest progress in humanity's understanding of love. However, recently endocrinologists, who were never considered very romantic, have challenged this notion, and now rather have a lot to say about how and why people love each other. Research is also shedding light on some of the more extreme forms of sexual behavior. And, controversially, some endocrine scientists see hormonal manipulation as the doorway to a future where love is guaranteed, because it will be provided chemically, or even genetically engineered from conception.
The scientific tale of love begins innocently enough with voles. The prairie vole is a sociable rodent, found in the woodlands of Europe and Asia, one of the only 3% of mammal species that appear to form monogamous relationships. Mating between prairie voles is a tremendous effort which takes almost 24 h, following which they bond for life. They prefer to spend time with each other, groom each other for hours and at end, nest together. They avoid meeting other potential mates.
However, another vole, a close relative called the montane vole, has no interest in partnership beyond one-night-stand sex. What is intriguing is that this major difference in behavior in two vole species, which are more than 99% genetically alike, is just because of a handful of genes, which affect their endocrine function.
The details of the vole story are fascinating. When prairie voles have sex, two posterior pituitary hormones, oxytocin and vasopressin, are released. If the release of these hormones is blocked, prairie-voles’ sex becomes a fleeting affair, similar to that normally enjoyed by their montane cousins. Conversely, if prairie voles are given an injection of the hormones, but prevented from having sex, they will still form a preference for their chosen partner.
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Does this mean that an injection of oxytocin can make prairie voles fall in love? Or that it encourages monogamy? A clue to what is happening, and how these results might bear on human behavior, was found when oxytocin was administered to the montane vole. It was found to make no difference. It turned out that the monogamous prairie vole has receptors for oxytocin and vasopressin in brain regions associated with reward and reinforcement, whereas the philandering montane vole does not.
The million rupee question: do humans have brains similar to prairie voles? Interestingly, there is no research to establish whether humans make a part of the faithful 3% category of mammals which prairie voles belong to, and which exhibit fidelity to partners.
So, what have reproductive endocrinologists contributed to the demystification and understanding of love and lust? They found that the oxytocin: the hormone of labor is also the hormone of love. It took no time for oxytocin to acquire fancy names such as “the bonding hormone,” “the cuddle hormone” and even “the love hormone.” And giving meaning to its new founded names, it generated the lust for money and resulted in products like “trust elixir,” an oxytocin-laced perfume being made available in many parts of the world []. However, concerns were raised that the oxytocin should not be abused as a recreational drug such as “ecstacy.” This was because oxytocin is not unlike the drug ecstasy, which triggers the release of serotonin, dopamine and oxytocin in the brain and heightens users’ feelings of trust and intimacy, even among complete strangers. Fortunately, the concerns seem unfounded given that the hormone does not produce a “high” as do other drugs of abuse.
In this review, we shall trace the orgasmic history of oxytocin, from the days of its birth to its present day status, and take a look into its future.
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The orgasmic history of oxytocin: Love,
It was in 1895 that Oliver and Schäfer discovered the first biological effect of the pituitary gland.[] They found that the extracts of the pituitary when injected into mammals raised their blood pressure---the pressor effect. Howell showed a few years later that this activity resided in the posterior lobe.[] Since that time, other biological activities of posterior pituitary extracts were noted, particularly the uterine-contracting or oxytocic effect by Dale in 1906;[] the milk-ejecting effect by Ott and Scott in 1910;[] the blood-pressure-lowering effect in birds, the so-called avian depressor effect by Paton and Watson in 1912;[] and the inhibition of urine excretion in man, the antidiuretic effect by Von den Velden in 1913.[] It was indeed initially thought that oxytocin was devoid of pressor and antidiuretic activity. However, it was later found out that both the pressor and antidiuretic activity, were inherent properties of the oxytocin molecule.[]
In 1906, Sir Henry Dale found that extracts from the human posterior pituitary gland contracted the uterus of a pregnant cat.[] He coined the name oxytocin from the Greek words ωχνξ, τoχoxξ, meaning “swift birth.” Sir Henry Dale also worked on histamine and acetylcholine among others and was jointly awarded the Nobel Prize in 1936 “for discoveries relating to chemical transmission of nerve impulses.” Forty seven years after Dale discovered it, oxytocin, a nine amino acid CNS neuropeptide, was the first ever polypeptide hormone to be sequenced and synthesized. It was done by Vincent du Vigneaud and for this achievement he was awarded the Nobel Prize in 1955.[]
Few people would know that the works of Vincent du Vigneaud on oxytocin were a result of his original interest in insulin. At no less an occasion than the Nobel Lecture which Vigneaud delivered on the 12th day of December in 1955, he brought out that oxytocin was a result of a “trail of sulfa research.” Vincent du Vigneaud described oxytocin as the principal uterine-contracting and milk-ejecting hormone of the posterior pituitary gland. Its synthesis was the culmination of a trail of research stemming from his original interest in sulfur and in insulin, a sulfur-containing compound.
It was enthusiasm of Professor H.B. Lewis in sulfur at the University of Illinois that aroused the interest of Vigneaud in the biochemistry of sulfur compounds. In 1923, W. C. Rose who succeeded Lewis as professor of biochemistry at Illinois, gave an account of the exciting discovery of insulin by Banting and Best, in a lecture he delivered on his return from a meeting in Toronto. This initiated Vigneaud's interest in insulin. Interestingly, at that time it was not even thought of that insulin would eventually turn out to be a sulfur-containing compound. However, interest in diabetes lead to the study of the structure of insulin which finally directed to work on the posterior pituitary hormones. Oxytocin was isolated from lyophilized posterior lobes of beef pituitary glands.[]
This discovery culminated in 1952 in the isolation of a crystalline flavianate of oxytocin with Pierce,[] the first crystalline derivative of this hormone to be isolated. It is of interest that an oxytocic fraction was also obtained from hog posterior pituitary glands which had a distribution curve approximately the same as that from the beef glands.[] In addition, the oxytocin obtained from the hog pituitary had the same amino acid composition and potency as that obtained from beef. The synthetic product was found fully effective in stimulating labor in full term women, and in milk ejection, and could not be distinguished from the natural oxytocin in its action. Approximately 1 μg of either the natural oxytocin or the synthetic material given intravenously to recently parturient women induced milk ejection in 20-30 s.[]