Posts Tagged ‘Hypothalamus’

The HPA axis: an introduction

I have been serving up diatribes for several weeks now.  It’s time to bring it back to physiology for a while.  I feel this way especially because I am so interested in how we might best mitigate hormone dysfunction.  One way is by investigating the means by which cells communicate to each other.   The HPA axis, for this reason, is a very big deal.  From my perspective, for those of us who suffer hormonal imbalances, it is the most important part of our bodies to pay attention to. Here’s why:

If our cells are a kingdom, and our hormones the governors, and leptin the bitchy king, then the HPA axis is the divine law that enables and justifies the whole damn thing. Or we could call it the flashy green code of The Matrix. Or the binding of a book. The point being that when the HPA axis is good it’s good, and when it’s bad all the king’s subjects die. No one wants to die. How do we stop everyone from dying?

The abbreviation HPA axis stands for Hypothalamic-Pituitary-Adrenal axis. It is sometimes called the Limbic Hypothalamic Pituitary Adrenal axis, and also the Hypothalamic Pituitary Adrenal Gonadotropic axis. (Gonadotropic, ladies!) This axis describes the complex interaction between the vast diversity of your hormone hubs, via direct influences and feedback mechanisms.

The Hypothalamus

The hypothalamus, at the core of our brains, is the primary point of connection between the central nervous system and the endocrine system. The hypothalamus releases hormones into the bloodstream. Some of them act on distant tissues, but others go directly to the pituitary gland and in turn tell it what to do. This is why it is often said that the hypothalamus controls the pituitary gland. 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 and adrenal gland. Hence why they are called “releasing” 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 TSH–thyroid stimulating hormone–so without this the thyroid gland does not produce what you need. Dopamine inhibits prolactin release, which also acts on the ovaries. 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 those distant-action hormones (ADH and oxytocin) which are less relevant for the axis. The anterior pituitary is the one that produces the relevant hormones. Follicle stimulating hormone stimulates the development of follicles on the ovaries and the production of estrogen. Luteinizing hormone triggers ovulation. TSH stimulates production of T4 and T3. In all cases, it’s clear that the receipt of stimulating hormones from the hypothalamus to the pituitary is crucial for reproductive function.

So direct central nervous system stimulation affects pituitary function. One example of this is circadian rhythms and the release of adrenocorticoid to stimulate waking. Yet there is another mechanism that tells the pituitary what to do, and this is feedback from its own system. The hormones directly secreted by the pituitary indicate to the pituitary how much of the product is in the bloodstream. This acts on the pituitary, but also on the hypothalamus, such that high estrogen, progesterone, and testosterone levels can all inform the hypothalamus to reduce production of GnRH. This is helpful often. But in other cases it is absolutely NOT, since high testosterone levels can inhibit GnRH in general, which reduces the production of all pituitary hormones.

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? If we are not constantly stressed, then 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.  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.  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.

4.  Cortisol also decreases REM sleep significantly: high concentrations in the blood can cause insomnia and, duh, decrease mood. Cortisol secretion increases in response to stressful stimuli. It is in fact crucial for survival in extreme circumstances. The reasons for this are not well understood, especially in light of the fact that cortisol inhibits immune function. The best guess is that cortisol is required for initial metabolic responses to stress–but that, right, we overdo it. Surprise.

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.) Spikes in cortisol about half as large as though during waking occur each time you eat, roughly correlated to how much you eat. DON’T freak out about your meals because of this. Your body handles cortisol quite well. No irrational panics allowed. Just– take note. This is one reason why both grazing and bingeing are not optimal behaviors.

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. You understand, then. The HPA axis is a delicate flower.

Finally, there is a whole class of adrenomedullary hormones, such as catecholamines (epinephrine and norepinephrine), we haven’t talk about. But they’re important, too. The first step in their biosynthesis is catalyzed by tyrosine. Don’t be in tyrosine (an amino acid). It’s important.  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.  Ack, ack, ack.

So that’s a review of the HPA axis.  It’s complicated as all hell.  But even more than complicated, it is 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.  I’ll talk about those issues in my next post.


04 2012