Many hormones are involved in social behavior, some of which are presented on this webpage. We selected oxytocin, dopamin, vasopressin, testosterone and estrogen.
Oxytocin
Oxytocin is considered as both a hormone and a neuromodulator. Oxytocin is involved in multiple functions: childbirth, sex thrive, and social behavior. It is a nine amino acid peptide produced by the paraventricular nucleus and supraoptic nucleus of the hypothalamus. The posterior lobe of the pituitary receives axonal projections from the hypothalamus and oxytocin is released by the neurohypophysis. In addition, oxytocin neurons originating from the PVN form projections with other parts of the brain such as the amygdala, the hippocampus, the nucleus accumbens and the ventral tegmental area.
What triggers the release of oxytocin?
This neuropeptide is released in response to psychological, social and even physical stressors. Oxytocin inhibits neurons in the amygdala that connects to other brain regions associated with fear such as the anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPC). One of the roles of oxytocin is to reduce the activation of ACC and MPC and thus reduces social anxiety. CD28 is the cyclic ADP ribose nuclease which is a glycoprotein localized at cell’s surface and is know to control oxytocin release.
Production of oxytocin
Oxytocin is mainly synthesized in the PVN (paraventricular hypothalamic nucleus) and supraoptic nucleus (SON), stored in the Heering bodies and released into the systemic circulation from the posterior pituitary. ADP-ribosyl cyclase activity is high in the hypothalamus and in the posterior pituitary. The lack of CD38 results in the decrease of ADP-ribosyl cyclase activity and thus lower cADPR formation which leads to alterations in OXT secretion in the hypothalamus and the pituitary. When it is released the oxytocin mainly binds to its receptor but it also has a weak affinity for the vasopressin receptor. Oxytocin binds to an oxytocin receptor known as OXTR, which belongs to the G-protein coupled seven transmembrane receptor family.
Histology
Oxytocin is released by the axon terminals of the neurohypophysis in so-called Herring bodies. On electron microscopy images, these are dilated areas in the terminal portion of axons with clusters of neurosecretory granules (containing oxytocin, antidiuretic hormone and neurophysins). Herring bodies often lie close to capillaries, which can be seen on the following image showing the axon terminals of the neurohypophysis.
Causes
Differences in socio behavioral phenotypes are due to genetic and epigenetic causes.
Genetic regulation
Alterations of genes involved in oxytocinergic signaling could be associated with differences in socio behavioral phenotypes. Principally:
- OXTR: gene coding for the oxytocin receptor
- CD38: oxytocin pathway gene
- OXT: gene coding for oxytocin itself
- AVP: gene coding for vasopressin production
In particular OXTR SNPs (single nucleotide polymorphisms) are associated with structural and functional alterations in limbic circuitry involving the amygdala, the hypothalamus and the cingulate gyrus.
1.Variants in rs53576 allele could be associated with:
more risk for autism, less maternal sensitivity, more feelings of loneliness in healthy females, lower positive affect in male, lower sociability and reliance on social approval and learning from interpersonal feedback
2.Variants in rs2254298 allele could be associated with:
Risk of autism spectrum disorders (ASD), anxiety and depression.
Epigenetic regulation
There are evidence that OXTR methylation may be dynamically regulated by psychosocial stress exposure, and it is associated with high callous unemotional (CU) traits and differential activation of brain regions involved in social perception. Some investigations of hepatoblastoma cell line shown that the methylation of the OXTR CpG island functionally suppresses transcription. It was also identified a region of the OXTR CpG island, termed MT2, which seems to be responsible for most DNA methylation-induced silencing of these constructs.
Oxytocin disorders
Oxytocin disorders are mainly found in autism, depression and anxiety. It has been shown that a high level of oxytocin is correlated to a healthy social behavior. On the contrary low levels of oxytocin lead to a deficit in social behavior. To treat oxytocin disorders, physicians recently developped intranasal admninistration of oxytocin. Moreover, sildenafil has shown a positive effect in oxytocin levels.
Dopamine
Dopamine dictates the behavior of individuals through the pathway of reward/prediction which is responsible for motivation. Due to evolution, some activities that help for the survival for the individual or his offspring such as eating and sex are made pleasurable.
Dopamine receptors
The binding of dopamine will activate the adenylate cyclase and then the protein kinase A. Finally, transcription factors will be activated and lead to the transcription of regulated genes. Unlike D1-like receptors, D2-like receptors will inactivate the adenylyl cyclase and thus have an opposite effect on gene transcription.
Dopamine and behavior
Dopamine is related to social behavior as it is involved in the reward-pathway. Indeed, dopamine is responsible for social motivation and guides individuals toward or away of achieving an outcome. High levels of dopamine produce a high level of activity and thus impulsive behaviors. On the contrary, low levels of dopamine lead to slow psychological activity.
Dopamine disorders
Dopamine disorders are mainly found in Parkinson’s disease, schizophrenia, anxiety, depression and psychosis. The causes of dopamine disorders can be due to drug abuse that modifies the thresholds required for dopamine cell activation. In addition the lack of proteins in the diet, in particular L-tyrosine which is used for dopamine metabolism. To treat these disorders, dopamine agonists are used as well as changing the diet.
Estrogen
Estrogen is a type of sex hormone involved in female reproduction and development of secondary sex characteristics. Estradiol is the most prevalent endogenous estrogens that have estrogenic hormonal activity.
Estrogen act via genomic or non-genomic cascades. When estradiol E2 binds to nuclear estrogen receptor ERα and ERβ, the receptor complex dimerizes and binds to estrogen response elements (ERE) promoting downstream gene expression reflects as the genomic pathways.
E2 can also promote the activation of rapid cascade via membrane bound receptors which involved MAPK activation and downstream targets such as ERK and CREB, representing so the non-genomic pathway. In particular increased the number of pERK–ir cells in the BNST(bed nucleus of the stria terminalis) and MEA(medial amygdala) under short days but not long days and pERK cell counts in the BNST and MEA were positively correlated with aggressive behaviors.
These rapid non genomic actions carried out by estrogens seems have important effects on behavior, with high dependence of environment.These behaviors are differently affected principally by three estrogen receptors (ERs), ERα, ERβ, and the G protein-coupled ER 1(GPER1)
Experiments on rodents, quail and songbirds show that environmental features such as photoperiod (day length), endocrine disruptors and phytoestrogens impact the pathways involving estradiol.
Aggressivity
Rapid effects of estradiol on aggression was seen in rodents with winter like photoperiods and, through analyses on genes controlled by estrogen response elements (ERE) in the promoter region, it was seen that short day photoperiods inhibit estrogen-dependent transcription in neural networks controlling aggression.
It was principally evidenced that lacking ERα lead to a reduced aggression, instead of lacking ERß which causes higher levels of aggression as compared to wild type mice. Photoperiod induce changes in nuclear estrogen receptors are not directly responsible for the effects of short days aggression but more closely linked to short-day induced decreases in circulating testosterone.
These effects of photoperiod are independent of changes in gonadal hormones, so the behaviourally active estrogens are probably synthesized in the brain.
Sexual behavior associated with aggressivity:
Sexual behavior and aggression are highly associated. Estrogens have rapid effects on mating behaviors and several experiments on male rats and comet goldfish shown as estradiol administrations induce in only 15-30 minutes copulatory behavior; mice spend more time in proximity to a female (higher proximity score).
Local estradiol synthesis, and/or conversion of testosterone to estradiol via aromatase activity are the pathway through which sexual behavior is mediated.
Learning and memory
ERα agonist but not ERß one, rapidly facilitate social recognition behavior in mice, suggesting a role of ERα as mediator of rapid effects of estrogens on learning behavior. There are also evidences that ERα mediate rapid effect of estrogen on hippocampal morphology, working at extracellular site could rapidly affect LTD, long term depression.
Environmental factors: phytoestrogens and endocrine disruptors
Many plants produce estrogen-like composite and also many industrial chemicals have estrogen like properties. In particular, corncob bedding is becoming one of the most wide-spread sources of phytoestrogens. Phytoestrogens such as isoflavone can affect behaviors mediated by the rapid action of estrogens; in particular phytoestrogens may be acting as an ER antagonist to affect sexual behavior in rodents.
Furthermore, exposure to endocrine disruptor such as Bisphenol A (BPA), a major component of many plastics, was found to increase aggression in mice and rats. Its effects can be especially long lasting, because these compounds can induce long lasting changes in DNA methylation in the brain.
Testosterone
Testosterone is a steroid hormone and is the primary sex hormone in males. It plays an important role in the development of male reproductive tissues and promotes secondary sexual characteristics such as increased muscle and bone mass and the growth of body hair. Its biological effects are mediated through the androgen receptor, where binding of testosterone ultimately results in changes of gene expression. Testosterone also regulates sex drive (libido), fat distribution and the production of red blood cells and sperm in adults. This hormone was also found to be involved in social behaviors such as relationships, mating, but also aggression and criminality.
Romantic relationships
Testosterone plays important roles in human romantic relationship dynamics. It promotes mate pursuit at various timescales and may increase the odds of entering in a relationship. Testosterone levels increase after exposure to potential mates, whereas investment in parenting and marriages predicts declines in testosterone. Elevated testosterone may predict reduced relationship satisfaction and commitment. Testosterone levels have been measured in females and males falling in love. They were increased in females and decreased in males compared to control groups. This difference in testosterone has been suggested to results in the temporary reduction of differences in behavior between the sexes.
Agression and criminality
It has been shown that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus in testosterone treated animals. A recent study using a pharmacogenetic approach found that testosterone increased aggression in men and effects were enhanced for men having a polymorphism in the AR gene associated with increased AR efficiency. Thus, testosterone appears to promote human aggression through an AR-related mechanism. Furthermore, effects are mediated by subjective reward associated with aggression and it is thought that testosterone regulates this reward through dopaminergic pathways.
Vasopressin
Vasopressin (arginine vasopressin, AVP; antidiuretic hormone, ADH) is a peptide hormone formed in the hypothalamus, then transported via axons to the posterior pituitary, which releases it into the blood. It plays a role in regulating the volume of water in your body and also affects blood pressure. Vasopressin receptor subtypes are expressed in different tissues, and their genes are located on separate chromosomes. Its biological effects are mediated through three receptor subtypes. The V1aR found in nervous system and throughout the cardiovascular system affects a broad set of behavioral functions. The VP V1b receptor is not only found in the pituitary but also in brain areas with a role in the management of stress and aggression. The VP V2 receptor is localized primarily to the kidney with a classical role in fluid balance. Though AVP may play an important role in the abnormality of the body-fluid balance in some of these conditions (Congestive heart failure, Liver cirrhosis, Chronic renal failure), they can also support sympathetic arousal, mobilization (fight–flight responses) or in more extreme cases a metabolically conservative, shutdown response. Thus, under conditions of extreme stress or trauma, VP may take precedent over OT and over survival strategies that are more prosocial or mobilized.
Autism
Recently finding suggest vasopressin as a possible biomarker/target for treating autism spectrum disorders (ASD), which are characterized by social, behavioral and communication impairments. If the hormone is indeed treated differently by the receptors in the male brain compared to those in the female brain, that’s all the more relevant for autism. Studies performed with children found varying levels of vasopressin did predict how well children in the autism group performed on a test of “Theory of Mind” – the ability to perceive the perspectives of others. Specifically, autistic children with low vasopressin levels performed poorly on this test. In children without autism, low vasopressin levels were not linked to worse results.
Anxiety
Several studies have shown that increased levels of vasopressin plays a role in the development of memory necessary for the avoidance of danger or survival . There is also experiments suggesting that it also regulates psychological processes linked with anxiety and obsessions. Anxiety in turn can reduce the capacity to use cognitive abilities to manage stressful experiences. Vasopressin’s mechanistical role also reveals the possible association of anxiety and ruminations with cardiovascular risk. Further the hormone plays a central role in circadian rhythms and is likely to be important in sleep disturbances or elevations in blood pressure, which are also common following stress and considered defining features of posttraumatic stress (PTS) disorders. Its role also explaing the emotional mobilization that one achieves in the body and the vigilance needed for guarding a partner or territory as well as other forms of adaptive self-defense.
Quiz
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