Melatonin Turns Down Your Stress Response

Melatonin Turns Down Your Stress Hormone Response

We know melatonin is our sleep hormone. And we know it plays a role in changing the Warburg metabolism that favors cancer through its effect on the PDC complex. But did you know that it also plays a big role in changing your metabolism of catecholamines, your stress response hormones? That is an interesting story.

Where that inhibition takes place is its own curious biology. Our adrenal glands make cortisol and catecholamines, epinephrine, and norepinephrine. We need cortisol to mobilize glucose and have an alert, awake brain, so it has also been included in the "stress response" portfolio. Cortisol also has a powerful diurnal pattern surging some 5-10 fold between 3 am and 7 am. That is the opposite of melatonin which surges with the onset of darkness and the dropping of cortisol levels.

How does melatonin turn down the production of catecholamines? Clearly we see melatonin go up as cortisol goes down. This is where the complexity and interwoven nature of our biology is so interesting. A whole family of peptide hormones called bone morphogenetic proteins, discovered around bone growth and actually being used clinically to help repair long bone fractures and recalcitrant dental problems, appear to be active in the core of the adrenal gland, where you make your stress hormones. The investigators in this study measured the messenger RNA of the rate limiting step of catecholamine synthesis, tyrosine hydroxylase and found that melatonin turned down its production. A bone-modulating protein, collaborating with melatonin to alter the production of catecholamines! Wakes you up in the morning. Puts you to bed at night.

The technology to elucidate all this intricate web is the same tool molecular biologists are using to examine COVID's effects on our immune system and that Shoemaker is using to examine the downregulation of mRNA in mitochondria secondary to CIRS and mold exposure. It's the measurement of tiny variations in messenger RNA, being sent around the body in the blood to activate and produce new protein. The enzyme, Polymerase Chain Reaction, can copy DNA and RNA and can make millions of copies. When you do that, you can amplify and study it and demonstrate increases and decreases in messaging that is happening in the human cell. And hence we can learn the subtle shifts and machinations of our own biology, and the intertwining effects of hormones.

www.What will Work for me. I'm taking 20 mg of melatonin at bedtime now and feel like I sleep pretty well. Could I be a bit more mellow from doing so? This paper suggests that my stress hormones are all downregulated by my melatonin dose. In the middle of the night, when monkey chatter wants to take over my brain, that effect may be what keeps me asleep. We do know that our production of melatonin has dropped by some 70% from childhood by the time we reach 60-70 years of age. So, I'm going to keep taking it.

References: Jr Ster Biochem Mol Bio, Wikipedia, 

Pop Quiz

1. Melatonin is known to reduce catecholamine synthesis. What are catecholamines?                       Answer: Your fight-or-flight hormones: epinephrine and norepinephrine.

2. How does it do that?                         Answer: Very complex interaction with BMP, bone modulating protein in the core of the adrenal gland. For a deep rabbit hole experience, read the Wikipedia entry on bone morphogenetic protein.

3. Does this make sense to you? If you are very angry, or frightened, common feelings with high catecholamine synthesis, can you sleep?                        Answer: Ah. No.

4. How did bone morphogenetic protein get involved in all this?                          Answer: This is just another example of the incredible, nuanced web of hormonal mechanisms we have yet to fully appreciate. We can't explain it. We can observe it.

5. I should take more melatonin?                     Answer: Probably. No harm, no foul.