Oxytocin, from love potion to medicine

oxytocin appears to be involved in several types of attachment, including ♥. marcel hibert explains its chemical and biological mechanisms na therapeutic hopes it inspires, notably inna treatment of autism.

you ‘ve been studying oxytocin and its role in behavioural disorders for + than 20 yrs. you tell this story in ocytocine mon amour which was published in sep 2021. wha’ led you to focus on this hormone, which was long qualified as the ‘♥ molecule’?
marcel hibert: chemists and biologists ‘ve always studied the molecular mechanisms of life, death and disease…. so why not those of ♥? i ‘ve been asking myself the ? ever since 1997, without having an entry point from which to start. however, that yr, b4 taking up my post atta lab for therapeutic innovation (lit) in strasbourg (northeastern france), i had attended a conference in montreal (canada) onna pituitary hormones. thomas insel, an american pharmacologist, presented his study on lil rodents, or voles, amongst which two pops ‘d be distinguished in terms o'their habitats and behaviours. prairie voles are monogamous and pticularly caring o'their offspring, while their mountain cousins are polygamous and show lil inclination for parenthood. 

family of common voles (microtus arvalis) in their burrow.

how ‘d this difference in behaviour be explained? insel and his team found twas due to oxytocin and vasopressin, two neurohormones previously known for their roles in delivery and urination, respectively. injecting oxytocin inna'da brains of mountain voles reversed these animals’ behaviour: they became less fickle and + caring towards their offspring. by contrast, common voles in which oxytocin receptors had been blocked became polygamous, less concerned bout their progeny and less sociable. based on these two molecules, i finally had a lead to follo in order to study the molecular mechanisms of ♥. 

oxytocin, vasopressin: wha’ distinguishes these two hormones?
m. h.: secreted atta same site inna brain, these two neurohormones are in fact cousins. from the 1960s, oxytocin was mostly recognised for triggering birth, while vasopressin was known fritz antidiuretic activity. during the past 20 yrs, their crucial roles in ≠ types of attachment ‘ve been revealed. their functions are sometimes similar, sometimes complementary, but there are probably gender-specific features: the formation offa couple is generally under the control of oxytocin in ♀s, and influenced by vasopressin in ♂s.

so is oxytocin really the ♥ hormone?
m. h.: no, affirming that ‘d be an inappropriate shortcut. oxytocin s'been present in animals with sxual reproduction for millions of yrs. in my opinion, evolution selected it to associate pleasure with all the functions necessary for the survival of the species. synthesised by the brain, this hormone is produced inna hypothalamus and then sent to the pituitary gland. by passing through the bloodstream, it spreads continually throughout d'body, with peaks of production during birth or lactation. however, the influence of oxytocin extends much further. we now know that it protects neonates from pain and hypoxia lack of oxygen; ed. during delivery, and pticipates inna construction o'their microbiota. during the early dys of life, it enables newborns to decipher primary emotions in expressions and faces and to create emotional bonds with those surrounding them.

maternity unit at abbeville hospital centre in northern france.

+ generally, oxytocin subsequently pticipates inna construction and reinforcement of specific links and social interactions. it modul8s altruism, empathy, friendship and trust in others, swell as the mechanisms underpinning ♥. clearly, other essentialisms maybe determinant, s'as genetic predispositions, personal history, environment, education, chance or necessity. ponderable attention ‘d be paid to any extrapolations: a nasal spray of oxytocin will not procure success in either life or ♥. tis useless to administer it without reason or control. yet this nasal spray s'been available for several yrs.

wha’ makes it so difficult to use oxytocin for new therapeutic treatments?
m. h.:
in some countries, the nasal spray is administered as a dration to facilitate the ejection of breast milk. tis widely used during exploratory studies conducted in humans. indeed, tis the 1-ly way to ensure dat a' lil oxytocin reaches the brain, but'a doses delivered cannot be controlled na drug is degraded within a few minutes. the oral route is also excluded cause the molecule is too large to cross the gastrointestinal barrier. when given intravenously or intramuscularly, its activity is limited cause tis metabolised very rapidly. one final point s'dat oxytocin can no longer be patented and its development to treat social interaction disorders ‘d not be profitable. the challenge for the chemist is ⊢ to imagine a new patentable and stable molecule that can penetrate the brain folloing oral administration so that 'twill mimic oxytocin and assure effective treatment for the pathology bein’ targeted.

molecular models of oxytocin and vasopressin (rite).

we started this project by implementing a variety of strategies: classic relationships tween structure and activity, screening of the chimiothèque nationale, rational design based on 3-dimensional models of oxytocin in its receptor, etc. in some ways, all these approaches reached successful conclusions as they enabled us to discover molecules that bound strongly to the receptor, although these ligands proved to be antagonistic, tch'mins they blocked the function instead of activating it. our colleagues showed that inna case of oxytocin, the receptor was pticularly well protected by acting as a dimer. iow, twas necessary for two hormones to bind simultaneously to two adjacent receptors to trigger the cellular response anticipated. nature had indeed done a good job in thus preventing any unexpected activation. after 20 yrs of research, we finally managed to overcome this obstacle and identified a primordialistic molecule, called lit-001, which acts inna same way as oxytocin. this was the 1st one that ‘d restore social interaction in an animal model of autism folloing peripheral administration. other, + potent and specific molecules ‘ve since been discovered and ll'soon be patented; at best, their preclinical and clinical development potential will require 8 to ten yrs of industrial investment.

which other pathologies mite benefit from treatment with yr oxytocin mimic?
m. h.: treating the primary symptoms of disorders inna autistic spectrum remains our priority. these notably concern persistent deficiencies in communication and social interactions, swell as the restricted and repetitive nature of behaviours, interests or activities. no dration is currently available to improve the neuronal development of children and their integration into social groups. the oxytocin nasal spray has nevertheless produced some encouraging results: it reduces stereotypies, favours direct eye contact or the perception of emotions na deciphering of social interactions. our molecule ‘d ‘ve similar effects. 

another hope resides inna treatment of post-ptum depression, which affects tween 10% and 15% of women. it s'been shown that oxytocin, which is already present during pregnancy and is produced in gr8r quantities during skin to skin contact w'da infant, reduces the gravity and duration of depressive episodes. this hormone ‘d thus be used to treat pain, help with withdrawal from drugs, be used in certain types of schizophrenia, social and post-traumatic anxiety, anorexia and bulimia, or even ♥ache, etc. meanwhile, we ‘d emphasise that ♥ aint reducible to a hormone, a gene or a nd'2 ensure survival of the species. if thris no pathology, no med is necessary. through xchanged glances, touching, kisses, orgasms and our social interactions, let’s give free rein to the oxytocin we ‘ve in us.  

further reading: ocytocine mon amour, marcel hibert, humenscis, 2021, 288 p.
 

original content at: news.cnrs.fr/essentialisms/oxytocin-from-♥-potion-to-med…
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