The hypothalamus-pituitary-adrenal axis in sport and exercise – Ian Craig

When hormones go out of balance, many practitioners will simply try and support the most obvious gland. However, as Ian Craig observes, because the endocrine system is so inter-connected, in many cases it is appropriate to support the hypothalamus-pituitary-adrenal (HPA axis), and other associated axes.

If you open up pretty much any physiology textbook, you’ll be told that the pituitary gland is a pea-sized gland that works alongside the hypothalamus, and together they regulate the function of the thyroid, adrenal and reproductive glands. You may also be told that these glands share in the control of somatic growth (growth hormone), lactation and water metabolism.

Anatomically, the first thing you may notice when you look at a picture of the pituitary gland (see banner image) is that it looks like a pair of testicles hanging down from the body; only, in this case the body is actually the hypothalamus and they are both found deep inside the brain. Or that visualisation may just be the male mind in action: accidentally or not, however, these pituitary lobes play a crucial role in sexual health!

It is important to note their anatomical location in the body – situated at the base of the central brain and at the top of the brainstem; the hypothalamus-pituitary unit is perfectly positioned to pick up messages from the unconscious part of the brain (limbic system) and to stimulate somatic physiology via its hormonal outputs. Many scientists label the hypothalamus and pituitary glands as simply the distal expression of the endocrine system, but they are too close to the brain for such a simple description.

The hypothalamus and pituitary are certainly the master controllers of our hormones, but I would suggest much more than that: they interplay with our unconscious thoughts and emotions, linking importantly between mind and body and forming what is known as the neuroendocrine system. This concept is also supported when we examine the blood supply to and from the hypothalamus and pituitary glands: rather than the
 blood simply flowing ‘south’ and transferring their messages to the body, scientists are suggesting that blood can actually flow upwards from the hypothalamus and pituitary into the cerebro-spinal fluid without impedance from the blood-brain barrier (1). In terms of nervous supply, the hypothalamus receives inputs from the limbic system (containing hippocampus and amygdala), the neocortex, the eyes, and the thalamus. The thalamus is considered a kind of complex relay station between unconscious areas and functions in the brain and the cerebral cortex, which is involved in consciousness.

The pituitary gland is also influenced directly by pain, sleep, wakefulness, smell, emotions, and even thought. Although the nervous and endocrine systems are usually considered separately, the proximity of hypothalamic nerves with the autonomic nervous system means that hormone outputs of the hypothalamus coordinate closely with the activities of the sympathetic and parasympathetic nervous systems. Corticotropin-releasing hormone (CRH), in addition to being a hormone-releaser, is also now considered a neurotransmitter, which stimulates sympathetic nervous output from the brain and spinal cord, while concurrently inhibiting the parasympathetic nervous system (2).

Other than emotional stress, the hypothalamus-pituitary-adrenal axis
 (specifically that involving CRH) is also stimulated by the pro-inflammatory cytokines that are responding to trauma, infection and histamine (allergic responses) (3), and also exercise (4).

Endocrine cascade of the hypothalamus-pituitary-adrenal axis


The classic model of endocrine function is that hormones are produced in glands, released into the blood stream and act at some peripheral site. However, as more research is released, we realise that this situation is becoming more complex. Firstly, it’s known that major organs also release hormones. Secondly, it’s understood that many hormones (such as neurotransmitters) act on adjacent cells (paracrine system) and other hormones even act on the actual cell of origin (autocrine system).

But for a moment, let’s review the classic understanding of the endocrine system – a model that is still valid, as long as you recognise that it is just the start. Figure 1 is a simplified view, but one that is easy to visualise – the hypothalamus sends releasing factors to the pituitary, which then stimulates glands to produce and circulate hormones.

As you can see in Figure 1, which is from a medical publication (5), there are actually many HP axes that propagate the body. Directed from the hypothalamus through the anterior lobe of the pituitary, the gonads, thyroid and adrenal glands are indeed innervated. However, growth hormone from the pituitary also stimulates Insulin-like growth factor 1 (IGF-1) from the liver for growth, and prolactin also stimulates lactation in the breasts (when required). The posterior lobe of the pituitary, perhaps the lazy brother, only has two functions: Anti-diuretic Hormone (ADH) is closely involved in the body’s water balance via kidney function and oxytocin is a well-known ‘love’ hormone during child birth and lactation.

Despite this large remit of jobs for the hypothalamus and pituitary glands, the axis that receives most attention within functional medicine and nutrition, is the hypothalamus-pituitary-adrenal (HPA) axis. In the context of the modern world, this attention is certainly deserved because of the way that we currently run patterns of chronic stress. Every one of the axes shown in Figure 2 has a feedback loop – usually negative – so that over-stimulation of an organ will initiate a down-regulation of HP output. This is a basic homeostatic control, like many in the body. However, the problem comes when our head or body gets in the way: when somebody experiences chronic emotional stress, coupled with insufficient coping strategies, or when somebody is physiologically mal-aligned with their life tasks, the HPA axis can become over-burdened. Cortisol levels may remain inappropriately elevated due to consistent HPA axis stimulation.

Conditions that are associated with hypothalamus-pituitary-adrenal axis dysfunction include (6):


• • High HPA activity – chronic stress, melancholic depression, anorexia nervosa, diabetes, syndrome X (insulin resistance and related disorders) and pre-menstrual syndrome.


• • Low HPA activity – adrenal fatigue, chronic fatigue syndrome, fibromyalgia, post-traumatic stress, rheumatoid arthritis and auto-immune exacerbation.

Negative feedback loops from the adrenals that are over-ruled by the head

Within the context of medicine, the scenario of HPA axis over-stimulation, just described, might be seen in the situation of unremitting life stress or trauma, that ends up in adrenal burnout. However, as practitioners working with average western-living people who are seeking weight management support, improvements in health, or a more challenging training programme, we are seeing this endocrine disruption on a daily basis.

The way that I view this subject is that many individuals have a mind strength that is much more dominant than their body’s negative feedback messages; the head-strong athlete who must clock up a certain daily mileage or the CEO who must consistently hit certain budgets or industry standards. I’ve worked extensively with both of these types of individuals – athletically, they are chalk and cheese, but head-strong they are just the same. In this era we are also experiencing the ‘corporate athlete’ – the person who works hard in his or her job, plus also pushes the limits in training to participate in a Tough Mudder or an Ironman, or to compete with office mates in CrossFit or Military Style training, or simply because they have the (perhaps) naïve notion that training harder will help them to lose weight. In this instance, the body’s negative feedback requests are ignored by the unconscious mind because the person has a job to do, or a target to meet, or a race to compete in.

Taking this notion a step further; we actually now have evidence that excessive exposure to cortisol can actually damage the neurones in the hippocampus (limbic system) that mediate the negative feedback to the hypothalamus (6). In other words; not only are these stressed-out guys and gals not hearing the negative- feedback messages, but they’re also now not getting them. That is pretty serious news, because what has started as a mild overexertion can turn into a full blown adrenal exhaustion, hypo-immune and chronic fatigue scenario over time.

In this instance, it may not only be the adrenal glands that are becoming fatigued or exhausted, but any of the other hypothalamus-pituitary axes. I once worked with a Masters triathlete who was so badly overtrained that she ended up with a pituitary tumour, which is written up here.

Mum, dad and the three kids


Take a look at Figure 2. Second to a blood sugar curve, it is the diagram I have used most in my clinic. When I find adrenal, thyroid or gonadal dysfunction in a client, I draw this for them. I ask them to imagine a family where the hypothalamus and pituitary glands represent Mum and Dad and the adrenals, thyroid and gonads (ovaries or testes) are the three kids. I now ask them what happens in a real family setting when one kid is persistently naughty? That kid will tend to get a lot of attention, while the other two receive less. Nine times out of ten, in the type of clients that I see, the adrenals represent the child most demanding of attention. This is why I’ve drawn a heavy arrow to the adrenals and the (inhibitory) bar across the arrow to the thyroid and gonads.

The hypothalamus and pituitary glands only have a finite capacity for signalling, so in the instance of the ‘naughty’ adrenals, the HPA axis can be up-regulated and the HPT and HPG axes down-regulated. With persistent stressors, all the hypothalamus-pituitary axes, and the cascade of events below it, can eventually become depleted and therefore down-regulated. This may mean that the thyroid becomes under or over-active (sometimes lack of regulation, rather than lack of function). The symphony of luteinizing hormone (LH) and follicle stimulating hormone (FSH) that stimulate the ovaries or testes, based on the timely conducting by the pituitary gland, may start to play out of tune. This may be as simple as women experiencing a bit of PMS, or it can become a more complicated problem, such as polycystic ovarian syndrome (PCOS) or endometriosis. Men may experience lowered levels of testosterone, a scenario that seems to be becoming more common in executive and athletic men.

As evidenced by many men being successfully treated for low testosterone levels with the LH stimulating drug clomiphene, an under-functioning pituitary gland is often the source of the problem. Additionally, it has long been understood that women with stress, disordered eating and/or excessive exercise patterns, can induce oligomenorrhea or amenorrhea via deactivation of the HPG axis (7).

PCOS in women has also been associated with HP axis dysregulation. Some type of life stress may stimulate the over-production of CRP in the hypothalamus, which drives elevated cortisol levels (6). High cortisol levels can increase blood sugar levels, causing a compensatory hyper-insulinemia and resulting insulin resistance. Excessive insulin, in-turn, stimulates more ovarian androgen production: elevated insulin and androgens are both common imbalances in PCOS.

So, good regulation of the hypothalamus-pituitary axes is therefore important for steroid hormone production, which is essential for good athletic performance. But, it is not just about the HPA axis disrupting everything else. You’ll notice in Figure 3 that there are double-headed arrows between the three sets of glands. Treating the adrenals is important, and working with the hypothalamus-pituitary unit is crucial in most cases. Sometimes just calming and supporting the HPA axis is enough, but the imbalanced gland also needs support.

An example is a research study that studied two groups of young men: one group had their testosterone levels suppressed pharmaceutically, whereas the other group were put on testosterone replacement therapy. What the researchers found was that CRH stimulated cortisol was significantly reduced for the testosterone-replaced guys compared to the testosterone-depleted group (8). In a stress-induced state, cortisol can be preferentially produced from pregnenolone, compared to other steroid hormones, including testosterone. This process has been nicknamed the ‘pregnenolone steal’: although it has been criticised as over-simplifying a complex hormonal interaction (9), the notion that excessive stress can inhibit sex hormone production is an easy one to explain to clients. So by supporting peripheral testosterone levels, it is possible to take some of the pressure off the hypothalamus and pituitary glands to supply cortisol production. Of course, for long-term health, the actual stressors will need to be substantially reduced.

Supporting the HPA axis

So, hopefully what you’ve gleaned from this article, is that if you have any problems with any of the aforementioned endocrine functions, it’s not simply a case of supporting that particular gland – we need to support the entire outflow of the hypothalamus and pituitary glands.

It’s beyond the scope of this article to go into intervention strategies, but I’ll mention a couple of places to start. It has been demonstrated that diets high in glycaemic load (GL), not only increase insulin resistance, but shift the HPA axis towards sympathetic over-activity, causing increases in cortisol, ACTH and noradrenaline, plus decreasing heart rate variability (an important indicator of health) (10). So, like in many nutrition interventions, blood sugar regulation is an important place to start.

In terms of supplements; pituitary glandular products provide a very direct pituitary support, but may miss out other endocrine glands. Adaptogenic herbs (such as ginseng and maca) have traditionally been used as adrenal support, but they also support the entire hypothalamus-pituitary-adrenal axis (11), plus other axes, so may also be good therapeutic choices for other endocrine functions.

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