The Orgasmic History of Oxytocin - Love, Lust, and Labor

7/6/2021 The orgasmic history of oxytocin: Love, lust, and labor
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Indian J Endocrinol Metab. 2011 Sep; 15(Suppl3): S156–S161. PMCID: PMC3183515

doi: 10.4103/2230-8210.84851 PMID: 22029018
The orgasmic history of oxytocin: Love, lust, and labor

Navneet Magon and Sanjay Kalra1
Department of Obstetrics and Gynaecology, Air Force Hospital, Kanpur, Uttar Pradesh, India
1Department of Endocrinology, Bharti Hospital and B.R.I.D.E., Karnal, Haryana, India
Corresponding Author: Dr. Navneet Magon, Obstetrician, Gynaecologist and Endoscopic Surgeon,
Department of Obstetrics and Gynaecology, Air Force Hospital, Kanpur, Uttar Pradesh, India. E-mail:
[email protected]
Copyright : © Indian Journal of Endocrinology and Metabolism
This is an open-access article distributed under the terms of the Creative Commons Attribution-
Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Abstract
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!
Keywords: Endocrinology, history, labor, love, obstetrics, oxytocin, pitocin
Introduction
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183515/ 1/9
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.
Comparative Endocrinology
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.
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.
Endocrine Contribution
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 [http://www.verolabs.com/]. 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.
Early History
It was in 1895 that Oliver and Schäfer discovered the first biological effect of the pituitary gland.[1]
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.[2]
Since that time, other biological activities of posterior pituitary extracts were noted, particularly the
uterine-contracting or oxytocic effect by Dale in 1906;[3] the milk-ejecting effect by Ott and Scott in
1910;[4] the blood-pressure-lowering effect in birds, the so-called avian depressor effect by Paton and
Watson in 1912;[5] and the inhibition of urine excretion in man, the antidiuretic effect by Von den
Velden in 1913.[6] 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.[7]
In 1906, Sir Henry Dale found that extracts from the human posterior pituitary gland contracted the
uterus of a pregnant cat.[3] 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.[8]
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.[9]
This discovery culminated in 1952 in the isolation of a crystalline flavianate of oxytocin with Pierce,
[10] 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.[10] 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.[11]
Current Concepts
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. One
of the oldest applications of oxytocin as a proper drug is as a therapeutic agent during labor and
delivery. It is a stimulant widely employed to induce or augment labor, especially at term, when
adequate oxytocin receptors are present. It is also one of the principal uterotonic drug used to prevent
post partum hemorrhage.
However, recent studies have begun to investigate oxytocin's role in various behaviors, including
orgasm, social recognition, bonding, and maternal behavior. For this reason, it is now sometimes
referred to as the “love hormone” and many such names described earlier.
Social bonding is essential to species survival since it favors reproduction, protection against predators
and environmental changes, and furthers brain development.[12] Exclusion from the group results in
individual physical and mental disorders and leads ultimately to death, both in animal models and in
primitive human tribes.[13] Oxytocin and its receptors appear to hold the leading position among the
candidates for the substance of “happiness.” If not “happiness,” at least it now seems to be an important
brain compound in building trust, which is necessary in developing emotional relationships, a process
also referred to as social bonding. A recent study by Kosfeld published in Nature has demonstrated that
in people playing a money game, a nasal spray of oxytocin raised their trust, even in a stranger.[14]
Such findings do bring some hope in the treatment of social disorders such as phobia.[15] Furthermore,
oxytocin and its receptors have been found to be involved in a plethora of social and affective,
physiological and pathophysiological behaviors, ranging from attachment security, mating, paternal
behavior and motherhood to autism and obsessive–compulsive disorder.[12,16–20] Indeed, in the
Prairie voles, oxytocin released into the brain of the female during sexual activity is important for
forming a monogamous pair bond with her sexual partner. Vasopressin appears to have a similar effect
in males.[21] Plasma concentrations of oxytocin have been reported to be higher amongst people who
claim to be falling in love. Oxytocin injected into the cerebrospinal fluid causes spontaneous penile
erections in rats[22] reflecting actions in the hypothalamus and spinal cord. It shows that the “love
hormone” can have a role to cause erection during sexual arousal. Arletti and Pedersen separately
studied that oxytocin increases sexual receptivity and can counteract impotence.[23] This “cuddle
drug” can indeed make partners cuddle up, and can have a larger role in treatment for infertility in
future! Can it indeed increase the lust for love? Interestingly, at least two studies have found increases
in plasma oxytocin at orgasm---in both men and women.[24,25]
Oxytocin is responsible for bringing in what is specifically called as “maternal behavior.” If oxytocin
antagonists are given to sheep and rat females after parturition, they do not exhibit typical maternal
behavior. By contrast, virgin female sheep shows maternal behavior toward foreign lambs upon
cerebrospinal fluid infusion of oxytocin, which they would not do otherwise.[26]
Many studies done in the past 15 years have tried to study the relationship between autism and
oxytocin. In 1998, Modahl et al., in their study found significantly lower levels of oxytocin in blood
plasma of autistic children.[27] Five years later, in 2003, Hollander and associates found a decrease in
autism spectrum repetitive behaviors when oxytocin was administered intravenously.[28] Further in
2007, in another study Hollander et al., reported that oxytocin helped autistic adults retain the ability to
evaluate the emotional significance of speech intonation.[29] More work is definitely required to
investigate the role of oxytocin in autism, but present work is definitely showing a ray of hope in
finding a role for oxytocin in treatment of autism.
In addition to fundamental insights into the role of oxytocin in the CNS, an increasing number of
studies performed recently have shown the importance of oxytocin and its involvement, directly or
indirectly, in several pathophysiological disorders in the nervous system and other organs. Oxytocin
has been broadly discussed under the following titles: “oxytocin and addiction”; “oxytocin increases
trust in humans”; “oxytocin increases generosity in humans”; “search for autism treatments turns to
‘trust hormone’”; “being human: love: neuroscience reveals all”; “oxytocin: the great facilitator of
life”.[30–34]
Oxytocin does reduce cravings. Kovacs in a study demonstrated that when oxytocin was administered
to rodents who were addicted to cocaine, morphine or heroin; the rats opted for less drugs or showed
fewer symptoms of withdrawal.[35] Billings recently reported that oxytocin also reduces cravings for
sweets. This way, can it emerge as a weight reducing and deaddiction agent? Oxytocin is calming.
Even a single rat injected with oxytocin has a calming effect on a cage full of anxious rats.[23] Can it
be a silver streak in treatment of anxiety disorders!
Oxytocin has been found to act in pathologic processes far removed from reproduction and nervous
system as well. Links have been made between oxytocin administration and injury healing. Vitalo et
al., provide evidence that oxytocin injections had a positive influence on wound healing in isolated
reared rats.[36] Legros also has reported that oxytocin counteracts the effects of cortisol, the stress
hormone.[37] Less stress means increased immunity and faster recovery. This may open up vistas for
the use of this hormone in chronic ulcers.
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. Peripheral, hormonal actions of oxytocin are mediated by
specific, high affinity oxytocin receptors. The peripheral actions of oxytocin mainly reflect secretion
from the pituitary gland. The letdown reflex and the uterine contractions are both affected this way
only. Due to its similarity to vasopressin, oxytocin can reduce the excretion of urine slightly. More
important, in several species, oxytocin can stimulate sodium excretion from the kidneys, and in
humans, high doses of oxytocin can result in hyponatremia.
The Potential
Therefore, the potential of oxytocin for drug targeting is immense. While it brings some hope for
alleviating serious social disorders, the issue appears extremely complex to tackle, as the specificity of
action might be difficult to control.[38] Oxytocin has become an interesting tool, especially through the
design of oxytocin agonists and antagonists, and a potential candidate for drug research and
therapeutics in humans.
One of the main and now well-characterized peripheral oxytocin targets is the erectile tissues, i.e.,
corpus spongiosum and corpus cavernosum. Though it appears to be an indirect effect, oxytocin
injected in the rats induces penile erection.[39] Moreover, oxytocin is thought to be associated with
ejaculation by increasing sperm number and contracting ejaculatory tissues especially prostatic urethra,
bladder neck, and ejaculatory duct.[40] An interesting study has shown that oxytocin-stimulated
ejaculation is specifically mediated by vasopressin V1a receptors; following which V1a antagonists
have been proposed as a putative therapy for premature ejaculation.[41] Therefore, oxytocin may have
a role to play in management of male infertility.
Another promising therapeutic breakthrough in the next years could be the development of oxytocin-
based medications to treat altered nociception. At the peripheral level, oxytocin also seems to be a key
component in bone formation, glycaemia, male sexuality, cardiac differentiation, and nonregulated
cellular proliferation.
Conclusion
The story of oxytocin begins right before pregnancy, continues during birth and later, travels from the
brain to the heart and throughout the entire body, triggering, or modulating a full range of physiological
functions and emotions: happiness, attraction, love, affection, and hatred after stress. These are all
governed directly or indirectly, at least in part, by oxytocin. The multidimensional nonapeptide appears
to play a central role in social behavior, and emerging clinical trials seek to assess and define its
therapeutic potential in the treatment of pathophysiological behaviors. Therefore, there is a strong
impetus to develop and establish new technological tools that will enable us to harness the full potential
of oxytocin and its congeners.
Taken together, the insights gained from more than 100 years of research indicate that the success story
of the hormone of “swift birth” will continue unabated. The potential therapeutic uses for oxytocin and
more long-acting and specific analogues of oxytocin are huge. Chemical, physiopathological,
psychological, philosophical, and ethical studies will reinforce the development of new drugs involving
the use of oxytocin, its agonists and antagonists for various human disorders such as autism, premature
ejaculation, osteoporosis, diabetes and cancer.
From an innocuous agent as an aid in labor and delivery, to being touted as the latest party drug,
oxytocin has come a long way. More research should be encouraged in this field in our country and
across the world. Awareness should be generated about the exciting history of this hormone among
reproductive and medical endocrinologists, just as it is for insulin.
It seems that during the course of the last 100 years, the hormone of love has had multiple orgasms. It
shall experience many more in the times to come. It has been documented that peak nocturnal uterine
activity at the end of gestation is because of the nocturnal peak in plasma concentrations of oxytocin.
[42] But is it also true that this nocturnal peak of oxytocin is responsible for other nocturnal stories
which culminate, nine months later, in keeping the obstetricians awake at night? Much more work
needs to be done to completely demystify the mystery of “oxytocin: the mystery hormone”, a new
name which can be added to the plethora of existing names this exciting hormone has already earned.
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
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7/6/2021 The orgasmic history of oxytocin: Love, lust, and labor

Indian J Endocrinol Metab. 2011 Sep; 15(Suppl3): S156–S161. PMCID: PMC3183515

The orgasmic history of oxytocin: Love, lust, and labor

Copyright : © Indian Journal of Endocrinology and Metabolism

Keywords: Endocrinology, history, labor, love, obstetrics, oxytocin, pitocin

Conflict of Interest: None declared.

6. Von den Velden R. Klin Wochenschr. 1913;50:2083. [Google Scholar]

8. Du Vigneaud V. Trail of sulfur research: From insulin to oxytocin. Science. 1956;123:967–74.

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