How cortisol is secreted in the brain

Remember what we read in the first cortisol post; cortisol is secreted from any perceived stress. This can be hearing the lion near us or it can be subtle, such as a job interview, which is what happens in modern times. Eating the wrong foods at the wrong times, pain in your body, blood sugar changes, emotional thoughts, overthinking things, worried about deadlines, etc. – all of these are perceived stressors. When we perceive a stress, we are going to trigger this cortisol release.

The Midbrain is Where the “Activating” Is

Stress is perceived at a primitive part of our midbrain, which is above the brainstem. So, when we look at the brain anatomically, we have the higher processing brain, the frontal lobe, all of those things that people see when they think of a brain. Below that, we have something called the midbrain and then the brainstem that connects to the spinal cord. Within the midbrain, there’s an area called the reticular activating system (RAS). The RAS is where we initiate the signal for stress or for cortisol release. Remember, physiologically speaking, a perceived stress is exactly the same as a real one.

Let’s go through the exercise. We think about something, perceive a stress, and we have some emotional thought. Once we perceive that stress, the RAS lights up and sends a signal to the next part of this chain, a higher up part of the brain called the locus coeruleus. The locus coeruleus is one of the smallest anatomical parts of the brain but is one of the most connected aspects of the brain. So, when that locus coeruleus gets fired upon, again we send a signal from the reticular activating system, the locus coeruleus sends a message to the hypothalamus saying it’s time to release cortisol. So, again, the chain of events is perceived stress, RAS to locus coeruleus, locus coeruleus to the hypothalamus, and then the hypothalamus sending a signal to the pituitary, and then the pituitary to the adrenal glands. You are likely familiar with the HPA axis. That is the hypothalamus-pituitary adrenal access.

The other interesting part about the locus coeruleus is that when its active, the neurotransmitter, norepinephrine is released. We’ll come back to this, but norepinephrine and cortisol are essentially partners in crime. Anytime we release cortisol, we also release norepinephrine; we perceive a stress, RAS goes to the locus coeruleus, locus coeruleus puts out some norepinephrine. We then trigger a signal to the hypothalamus, which signals the pituitary. The pituitary gland is an interesting part of the brain because it’s in charge of all the signaling molecules and hormones.

You may be familiar with hormones like TSH, LH, FSH, growth hormone. Each of those have releasing hormones and come from the pituitary or hypothalamus. For the adrenal glands, it’s called Adrenal Cortico Tropin Hormone or ACTH. So, the anterior or the front part of the pituitary puts out ACTH, which travels through the bloodstream to the adrenals and says, “put out cortisol and even more norepinephrine.” These are two places that we release norepinephrine (there are more). This is important because we can modulate those different pathways to help improve how we put out cortisol. To summarize, this all has to do with a perceived stress, reticular activating system, locus coeruleus, through the hypothalamus, pituitary gland, adrenal glands, and then comes out cortisol.

When we are chronically stressed over time, it wears down our adrenals, and our ability to put out enough cortisol. We can clearly see this on salivary cortisol tests. This is what happens to people in our modern-day world, we stop our ability of putting out enough cortisol, and what we end up having is unopposed norepinephrine. And the real-world significance is that people who are anxious or feeling stressed, are literally feeling the effects of unopposed norepinephrine. Many antidepressants are aimed exactly at decreasing this unopposed norepinephrine. This is an important process to understand and worth reviewing. It is also the reason why medications may help the symptoms, but do not do much to solve the problem.

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