The HPA axis: an introduction

The abbreviation HPA axis stands for Hypothalamic-Pituitary-Adrenal axis. Sometimes it is the HPAT or HPATO axis, standing for Hypothalamic-Pituitary-Adrenal-Thyroid-Ovary axis – depending on how expansive and inclusive you want your definition to be.

This axis describes the complex interaction between the vast diversity of hormone hubs, via direct influences and feedback mechanisms.

The HPA axis is responsible for an extraordinary number of important functions in the body, from libido to clear skin, to having energy, to sleeping and waking up, to hydrating, to regulating blood sugar, and to being able to menstruate and conceive children.

My book, Sexy by Nature, and Dr. Sara Gottfried’s book, The Hormone Cure, both provide additional details on how hormonal health is key to happiness and health.

The Hypothalamus

The hypothalamus is the key to the whole axis. It is the part of the brain that interprets how happy or stressed you are, as well as recevies signals from you body on your metabolic state, how well and recently you’ve been fed, your circadian rhythms, and the like. It is the “smart” part of the axis — it is the command center.

The hypothalamus is therefore responsible for releasing hormones into the bloodstream from the brain. In some ways it nearly completely controls the pituitary gland, as well as the adrenal and thyroid glands.

The secretion of hypothalamic hormones GnRH, gonadotropin releasing hormone, GHRH, growth-hormone releasing hormone, TRH, tryptophin releasing hormone, dopamine, somatostatin, TRH, thyrotropin-releasing hormone and CRH, corticotropin releasing hormone all influence the action of the pituitary adrenal and thyroid glands. They are the “green lights” that the hypothalamus sends to glands for the permission to produce their own sets of hormones.

The job of the hypothalamus is to conduct the orchestra. It asks for certain things to be played, and if all things are running smoothly, the whole orchestra plays in beautiful concert.

The hormones released by the hypothalamus have specific effects. There are a few that are more relevant for our purposes here: GnRH stimulates LH and FSH activity in the pituitary, which are directly responsible for ovarian activity, ovulation, and menstruation. TRH stimulates the release of T4 and T3–thyroid hormones–so without this the thyroid gland does not produce what you need. And CRH stimulates the release of adrenocorticopin, a precursor to stress hormones. We might say that CRH is the first line of activity in the stress response.

The Pituitary Gland

The pituitary gland is generally divided into two parts, the anterior pituitary and the posterior pituitary. The posterior pituitary releases distant-action hormones (ADH and oxytocin) which are less relevant for the axis.

The anterior pituitary is the one that produces the relevant hormones for reproductive function. Follicle stimulating hormone stimulates the development of follicles on the ovaries and the production of estrogen. Luteinizing hormone triggers ovulation. Both of these hormones signal to the ovaries when to produce estrogen and progesterone.

Hormone levels in the blood indicate to the hypothalamus how much should be produced in the future. This is called a “negative feedback loop.” The feedback is negative because if there is too much of anyone hormone, the body will produce less of it (or will at least try to) the next time around.

The Adrenal Glands

The adrenal glands consist of two distinct parts: the adrenal medulla, which secretes catecholamines directly into the blood, which I’ll touch on a bit later, and also the adrenal cortex, which secretes steroid hormones. The primary steroid hormones are cortisol, corticosterone and DHEA, the precursor to adrenal sex hormones.

Approximately 90 percent of the cortisol in our systems is “bound.” The remaining 10 percent is free, and it’s what is biologically active. Cortisol is metabolized in the liver, and it has a half life of 60-90 minutes! Isn’t that amazing? The hyper-stressed states we enter into from an immediate event are only supposed to last for 60-90 minutes. Amazing.

Cortisol is important for a number of reasons. Without it, we die. Here are some of its functions:

1. Metabolism.  Cortisol and other glucocorticoids exert anabolic effects– that is, gluconeogenesis and glycogenesis– on the liver, and catabolic effects– or proteolysis, and lipolysis– in the tissue. What this means is cortisol stimulates activity that utilizes energy sources. Proteolysis eats muscle tissue, which is generally bad, but lipolysis eats fat tissue, which is usually good. Gluconeogenesis and glycogenesis make glucose and glycogen in the liver.

2.  Blood sugar management. From the stimulation of cortisol, glucose output by the liver increases and glucose uptake by other tissues decreases. Another way to say this: cortisol increases blood sugar. Insulin is secreted in response to blood sugar, in order to mitigate the effects.

3.  Immune regulation. Cortisol influences the immune system and inflammatory responses. Cortisol and all other glucocorticoids suppress the synthesis of arachnidonic acid, the precursors to a number of compounds involved in the inflammatory response. They also decrease the key compounds interleukins and gamma interferon, which are crucial for the immune response.

In short, cortisol can reduce inflammation. (This is good in short bursts but should be avoided in the long-term.)

4.  Wakefulness (and insomnia). Cortisol decreases REM sleep significantly: high concentrations in the blood can cause insomnia and decrease mood. Cortisol secretion increases in response to stressful stimuli. It is in fact crucial for survival in extreme circumstances.

ACTH and cortisol are released in irregular pulse throughout the day. The biggest pulse occurs in the early morning, and starts a few hours before waking. The lowest levels of ACTH in the blood occur right around the time of falling asleep (in someone with regular circadian rhythms.)

This whole system is moderated by negative feedback, as in most of the body’s systems. When the hypothalamus detects enough cortisol, CRH (in the hypothalamus), and therefore ACTH (in the pituitary), and therefore cortisol (in the adrenals) production, are all decreased.

Finally, there is a whole class of adrenomedullary hormones, such as catecholamines (epinephrine and norepinephrine). Epinephrine and norepinephrine both increase blood glucose concentrations and metabolic rate. Epinephrine increases cardiac output, vasodiliation in skeletal muscle and liver but vasoconstriction in other vascular tissues– so essentially it shunts blood to skeletal muscle and the liver. Norepinephrine causes primairly vasoconstriction, which results in increases in blood pressure–ie, a reduction in cardiac output.

Epinephrine and Norepinephrine are activated by “fight or flight” situations, ie, our regular lives. Their production is, here’s another surprise, initiated by the hypothalamus. BUT these babies aren’t regulated by negative feedback. This is important. Cortisol will decrease in response to high cortisol levels. Epinephrine and norepinephrine instead can just keep on rising.

So that’s a review of the HPA axis. It’s important. The HPA axis runs the whole hormonal game, and therefore the vast majority of your reproduction and metabolism. It responds to stress, and it helps you mitigate stress. It responds to hormonal input, and helps you mitigate hormonal problems.  It is sensitive to signalling from all over your body. These are all awesome things, but it also means that disruptions, can really throw you off.

The HPA axis significantly effects your thyroid gland, how you metabolize food, how much estrogen and testosterone you produce in your ovaries, and how much stress hormones and sex hormones you produce in your adrenals.

For more on the way hormones affect your happiness and health – and what you can do about it – I recommend a couple awesome books:

-Dr Sara Gottfrield’s Hormone Cure

-My own best-seller on women’s health, Sexy by Nature