The HPA axis describes the interaction between the hypothalamus, the pituitary gland and the adrenal glands. The hypothalamus and the pituitary gland are located in the brain and the adrenal glands are found just above our kidneys. The HPA axis can be triggered by any stressor; this could be physical, environmental, emotional or endogenously produced (such as inflammation), I’m pretty sure mine is being triggered by writing this blog…#justsaying
When we first encounter a stressor, our sympathetic nervous system kicks in and this results in the secretion of adrenaline and noradrenalin (norepinephrine and epinephrine for our American friends) this causes those usual lovely stress symptoms such as heart palpitations, butterflies in your tummy (yes, that is scientific terminology) and perspiration. Almost concurrently the HPA axis kicks in – the hypothalamus responds to the elevated levels of adrenalin by secreting corticotrophin-releasing hormone (CRH/CRF). This is the message that the pituitary gland needs to play its part which is to secrete a substance called adrenocorticotropic hormone (ACTH). ACTH travels down to the adrenal glands where it knocks on the door and asks if cortisol can come out to play. Cortisol usually obliges.
Cortisol has a number of effects on the body; however, in response to stress it is secreted to help your body deal with the stress as best it can. It increases blood pressure and cardiac output (to stop you from fainting and keep you running from the stressor!) It increases circulating levels of glucose (blood sugar) which provides your body’s cells with fuel to keep going. In addition to increasing body responses that are beneficial to us during times of stress, it also decreases body responses that are not so beneficial to us such as our reproductive system and our digestive system (who’s ever stopped mid-bolting-away-from-an-axe-murderer because ‘they really need a poo’… our body’s are smarter than that!)
Our HPA axis is vital to our stress response system, we are undoubtedly going to be exposed to stress- it is life. However, that stress is supposed to be acute, short lived and we are meant to be harmoniously restored after said stress has past. So what happens when our HPA axis is made to work overtime, continuously? Or, the stressor we encounter is so traumatic we never feel like we ‘reset’? Or, heaven-forbid, our gut-bacteria is so out of whack that our meticulously in sync body cells, organs, neurotransmitters and hormones simply cannot communicate to each other the way they should? Well, quite frankly… disease happens. A chronic state of ill health that doesn’t have just one symptom picture- it can manifest in numerous ways.
HPA Axis and Our Health
HPA axis dysregulation can, unfortunately, occur relatively easily. Baseline activity of our HPA axis can become affected from as early as infancy and, even somewhat earlier due to the inheritance of our microbiome, which I’ll discuss later. However, animal studies have shown that post natal rearing conditions influence the development of the HPA axis. Prolonged maternal separation and an emotionally disconnected infant-maternal bond, where the child’s emotional needs are not parented, lead to the development of an over-reactive HPA axis later in life. Whereas this is not seen in infants that are reared in an emotionally stable and connected family and who have all of their emotional needs met (1).
Although this is such a vital time in our development and basically paves the way for how we will handle and cope with stress, it is not the only causative factor to a dysfunctional HPA axis. Any emotionally traumatic experience can dysregulate the HPA axis. You might not even be consciously aware of it- it could even be something like a severe illness or subtle chronic daily stress that ‘builds up’. Usually, from my professional experience, when I am speaking with someone that displays HPA axis dysfunction they might say ‘I’ve never been well since (insert specific event/illness here)’ or, ‘my childhood was tough, I always had a strained relationship with my parents…’, or, they are the classic Type A personality… we all know the ones- in fact, I’m sure we all have a little of Type A in us!
Conditions related to HPA axis Dysfunction
- Chronic stress
- Anorexia nervosa/Bulimia
- Metabolic Syndrome
- Thyroid conditions
- Chronic Fatigue
- Anxiety/panic disorder
- Obesity/inability to lose weight
- Irritable Bowel Syndrome
- Rheumatoid arthritis
- Insomnia/sleep issues
DHEA is also produced by the adrenal glands and is respondent to ACTH from the pituitary gland, just like cortisol. DHEA antagonises cortisol, meaning it inhibits or stops cortisol from doing its job. It also is a precursor for some of our sex hormones-like testosterone and the oestrogens and it requires cholesterol and pregnenalone (the progesterone precursor) for production, as does cortisol (2).So how exactly does the HPA axis have so much influence over our health? Well to cut a long story short and to save you many biochemistry lessons… the answer is Cortisol and its ratio relationship with the other hormones, specifically DHEA.
So think of cortisol and DHEA like two little buddies riding on a sea-saw, one goes up, the other goes down and vice-versa. They have opposing effects.
As we discussed above, our stress response system is designed to direct cellular processes away from our long term metabolic processes (think digestive and immune) and toward immediate survival (think energy) and then, rebalance or, homeostasis. However, obviously under HPA dysfunction, this is not the case. Instead, what we see is ACTH driving constant elevated cortisol, which can begin to deplete DHEA. This high cortisol phase may last years, and leads to an adaptation within the HPA axis which can ultimately lead to reduced, or ‘depleted’, cortisol and DHEA levels (it is suggested that this occurs to ensure long-term survival in an adapted HPA axis state from chronically elevated cortisol suppressing our immune system (3) (smaaaart!!))This is often referred to as ‘adrenal exhaustion/fatigue’; however, these adaptive changes are mainly being driven by the pituitary and the hypothalamus within the brain.
Ok, so I really promise you I’m tryna’ stay low key on the biochemistry stuff, so if you’ve made it this far…kudos! If you look at the box above of conditions related to HPA axis dysfunction (there are more btw!) it’s relatively easy to see how they can occur from HPA axis dysfunction (even though in modern medicine most of these ‘conditions’ are seen as their own ‘entity’, so the root cause is never addressed) but let’s look more closely anyway:
The Immune system is one of the primary systems affected by too much cortisol and that’s because our immune system remains suppressed while cortisol is elevated. HPA axis dysfunction and elevated cortisol can lead to the development of any type of autoimmune disease (think thyroid, eczema, psoriasis-anything really!) (3)
Elevated cortisol also inhibits our reproductive and growth systems and messes with the hormones that are needed for their correct functioning. Remember above how we spoke of DHEA and its relationship with cortisol and when cortisol is up DHEA is down, and DHEA is also needed to make some of our important sex hormones like oestrogen and testosterone. So if there is simply not enough DHEA we will not make enough oestrogen or testosterone. Also, remember how it was mentioned that pregnenalone is used to make cortisol, DHEA and progesterone? Well as you can imagine if the body has to pump cortisol out like a madman this can drive progesterone down as it gets shunned to the side lines, well really it’s getting made but going straight into cortisol production and not having any other chance to do its thang. This creates a whole mess for our sex hormones and can lead to low libidos in men and women, inability to get and maintain an erection in men, PCOS, oestrogen dominance, amenorrhoea and dysmenorrhoea in us women folk. And here’s the cherry on top of the (ketogenic) cake… guess what’s needed to make ALL of the above… cholesterol! So yep, our body generally goes into overdrive making cholesterol (9 times out of ten ‘high cholesterol’ as told to you by your GP is because your body is making too much! NOT because of what you’re eating, unless you eat lots of sugar! But that’s a blog for another day) to support the demands of all these hormones but also to dampen down the inflammation that occurs in this state! So guess what else happens… you get high cholesterol too.
Growth and reproduction are also influenced by thyroid hormone function which is adversely affected too in the cortisol HPA axis cascade (surprise surprise). Not only is our thyroid hormone inhibited, the conversion of our T4 to T3 is impaired also. And our T3 is a more active thyroid hormone (3).
Cortisol also increases insulin levels and this can lead to insulin resistance, diabetes, metabolic syndrome, obesity (especially a larger tummy area) and inability to lose weight. We don’t need to mention all the conditions that come along with these too such as high blood pressure and all of the cardiovascular risks.
DHEA actually serves to prevent systemic inflammation and protect parts of the brain (particularly the hippocampus) from cortisol. A reduction in DHEA and damage to other metabolic processes can lead to chronically inflammatory states (think fibromyalgia, Rheumatoid arthritis, IBS, chronic fatigue) as well as mood disorders due to the damage on the hippocampus- this is where the mental health stuff can come in as well as from neurotransmitter irregularities from our gut microbiota (3) (4) (5)
So who feels like they need a big dose of magnesium after reading this? I sure feel I need some after writing it! The intricate workings of our HPA axis are so fine and detailed and this is honestly only covering the tip of the iceberg… I just wanted you all to know how meticulously joined not only our hormones are, but our whole bodies! And, I haven’t even got to how the gut comes into play!
HPA Axis and the Gut Microbiome
The interaction between stress, the HPA axis and our overall health and immune system is fairly well established (although not commonly looked at in treatment). The gut microbiota has a role in mediating this interaction. The microbiome we inherit as infants does play a part in the development of our stress response system. Low levels of lactobacillus have been correlated with heightened response to stress. Babies born to highly stressed mothers, or who had an emotionally-disconnected attachment have been shown to have lower levels of lactobacillus and bifidobacterium and higher levels of proteobacteria. This sets them up for a pre-adapted HPA axis response (5).
Stress can also, very quickly, remodel the gut microbiota. Stress impacts on the development of our intestinal barrier and can increase gut permeability which can give rise to gut dysboisis and food intolerances, at the same time undiagnosed inflammation in the gastrointestinal tract (parasites, gut dysboisis, food intolerances) will drive HPA axis dysfunction, and this is because the body views this inflammation as a ‘stress’ so begins secreting cortisol (5).
And the cycle continues.
Lactobacillus species and Bifidobacterium species have been shown to not only suppress stress-induced changes in gut permeability, but also to dampen HPA axis activity (5).
So, when it comes to the vast array of effects that a dysfunctional HPA axis can cause… a really good starting point for optimal and long lasting treatment is….the gut!!! And this can be done concurrently while supporting the biggest presenting individual symptom picture of the HPA axis dysfunction.
Phew! Now, seriously…where is that magnesium?
- Liu D, et al, Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinephrine release in the Hypothalamic paraventricular nucleus, J Neuroendocrinol 2000, pp 5-12, https://www.ncbi.nlm.nih.gov/m/pubmed/10692138/
- Mitrovic, I, Introduction to the hypothalamic-pituitary-adrenal axis (HPA) axis (lecture)
- Guilliams, TG, Edwards, L, Chronic stress and the HPA axis: clinical assessment and therapeutic considerations, The Standard, 2000, vol. 9 No. 2 http://www.pointinstitute.org/wp-content/uploads/2012/10/standard_v_9.2_hpa_axis.pdf
- Keller, PA et al, The role of the HPA axis in Psychiatric Disorders and CRF antagonists as potential treatments, 2006, The University of Wollongong, http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1030&context=scipapers
- Kelly JR, et al, Breaking down the barriers: The gut microbiome, intestinal permeability and stress related psychiatric disorders, frontiers in cellular neuroscience, 2015, http://journal.frontiersin.org/article/10.3389/fncel.2015.00392/full