Vasopressin

Vasopressin, also known as antidiuretic hormone (ADH), is a neurohypophysial nonapeptide (containing nine amino acids) hormone found in most mammals^[1]. It plays a vital role in maintaining the volume and osmolarity of bodily fluids, but also has an interesting role in social behaviour^[2]. More on that later.

In humans, vasopressin is synthesised in the hypothalamus, specifically in the magnocellular neurons of the paraventricular and supraoptic nuclei^[3].

Here's how the process works from synthesis to release:

1. Biosynthesis: Vasopressin is synthesised as a precursor molecule called preprovasopressin in the cell body of neurons. This precursor also includes neurophysin II (a carrier protein) and a glycoprotein called copeptin.

2. Processing: Preprovasopressin is processed in the endoplasmic reticulum, where the signal peptide is cleaved, resulting in provasopressin. As this molecule moves through the Golgi apparatus, further enzymatic processes convert provasopressin into the mature vasopressin, along with neurophysin II and copeptin.

3. Transport: The mature vasopressin is stored in vesicles and is transported down the axons of these neurons to the posterior pituitary gland, where it is stored until it's released into the bloodstream in response to certain stimuli.

Vasopressin has several significant functions in the body:

1. Water Regulation: Its primary role is to regulate water balance. When plasma osmolarity (concentration of solutes) rises above a certain threshold, or when blood volume drops, vasopressin is released^[4]. It acts on the collecting ducts of the kidneys, making them more permeable to water. This allows more water to be reabsorbed back into the bloodstream, leading to a concentration of urine and dilution of the blood plasma.

2. Vasoconstriction: Vasopressin can cause vasoconstriction, or the narrowing of blood vessels^[5]. This helps increase blood pressure. While this effect is generally weaker than its antidiuretic action, in situations of severe blood loss, vasopressin release can help maintain blood pressure.

3. Other Functions: In high concentrations, vasopressin can also stimulate the release of factor VIII and von Willebrand factor from endothelial cells, which play roles in blood clotting^[6].

4. Influence on Behaviour: In the brain, vasopressin is involved in various social behaviours, including social recognition, bonding, and aggressive behaviours. This role is more pronounced in some animal models, like voles, where vasopressin differences contribute to variations in social behaviours^[2].

It is the latter which we will focus on.

Vasopressin's influence on behaviour, especially in the context of social interactions and bonding, has been extensively studied, mainly in animal models, particularly in the male prairie vole, which is essentially a glorified rat^[7].

Male prairie voles, which form monogamous pair bonds, have higher vasopressin receptor densities in the ventral pallidum region of the brain compared to montane voles, which do not form such bonds^[9]. Infusing vasopressin in the brain of male prairie voles enhances pair bond formation. Conversely, blocking vasopressin receptors can inhibit this behaviour. For this reason, vasopressin's impact is often compared and contrasted with that of oxytocin, another peptide hormone with significant behavioural effects^[10].

Additionally, vasopressin plays a role in rodent behaviour in the following ways:

1. Social Recognition: Vasopressin is essential for social recognition, which is the ability to recognise and remember individuals^[11]. In rodents, vasopressin seems to be crucial for short-term social memory. Blocking the actions of vasopressin impairs the ability of animals to recognise others they've recently encountered.

2. Aggressive Behaviour: Vasopressin can modulate aggressive behaviours, particularly in males. Increased vasopressin levels or enhanced vasopressin receptor signalling is often associated with heightened male-male aggression in several species^[12]. This is thought to be related to territorial and mating behaviours.

3. Stress Responses: Vasopressin is involved in the body's response to stress, particularly in the hypothalamic-pituitary-adrenal (HPA) axis^[13]. It can amplify the stress response by enhancing the release of corticotropin-releasing hormone (CRH) from the hypothalamus. CRH then stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary, which in turn leads to cortisol release from the adrenal glands. Cortisol is a primary stress hormone.

4. Parental Behaviour: There's evidence to suggest that vasopressin, along with oxytocin, plays a role in modulating parental behaviours^[14], although the exact mechanisms and manifestations vary among species.

5. Anxiety and Depression: Although the exact role is still being elucidated, there's evidence that vasopressin signalling may be linked to anxiety and depressive behaviours^[15]. Alterations in vasopressin receptors or signalling pathways have been implicated in certain mood disorders.

The behavioural effects of vasopressin are largely mediated through its receptors, primarily V1a and V1b receptors^[16]. These receptors are distributed in various regions of the brain, and their specific localisation can significantly influence behavioural outcomes.

Ok, so now we've looked at rodents. How about humans?

Although the bulk of behavioural studies on vasopressin has been conducted on animal models, particularly rodents, there's increasing interest in understanding its role in human social behaviours, emotions, and psychiatric disorders^[17]. Here's what we currently understand about vasopressin and human behaviour:

1. Social Behaviour: Similar to its role in voles, vasopressin appears to influence certain aspects of human social behaviour. For example, some studies have suggested that vasopressin can enhance social memory in humans, or the ability to remember and recognise faces^[18].

2. Aggression and Stress: Vasopressin might modulate aggressive behaviours and responses to stress in humans. Some research indicates that individuals with certain polymorphisms in the vasopressin receptor gene may exhibit different patterns of aggression or social behaviours^[19].

3. Pair Bonding and Attachment: While the evidence is not as robust as it is for voles, there are suggestions that vasopressin might be involved in human attachment and romantic relationships^[20]. Some studies have looked at vasopressin levels or receptor polymorphisms in the context of human partner preferences, bonding, and relationship behaviours^[20].

If you find this fascinating and want to know more, I suggest watching Dr. Robert Sapolsky's Stanford lecture on Molecular Genetics.