Let us dive into POMC biology, as it is one of the most important proteins found in the human body—tied to energy, light, nature, and circadian biology as well as appetite, bioenergetics, libido, hormones, pain modulation, stress response, mood, metabolism, and immunity.

Proopiomelanocortin (POMC) is an ancient polypeptide that gets cleaved into various peptides that influence our biology. To build optimal health, it is essential that POMC is cleaved correctly. This post will be a deep dive into POMC biology, its cleavage products and how to optimize it.

POMC is a precursor polypeptide with 241 amino acid residues. It is found in several regions of the body:

• brain regions
• the skin of the leg, torso, arms, etc.
• white blood cells
• adrenal glands
• heart
• sexual organs
• gut regions
• spleen
• pancreas
• muscle tissue

The full list of POMC locations in the body can be found here.

POMC acts as a precursor to several peptides:

• α-Melanocyte-Stimulating Hormone (α-MSH)
• β-Melanocyte-Stimulating Hormone (β-MSH)
• γ-Melanocyte-Stimulating Hormone (γ-MSH)
• Adrenocorticotropic Hormone (ACTH)
• Corticotropin-like Intermediate Peptide (CLIP)
• β-Lipotropin (β-LPH)
• Gamma Lipotropin (γ-LPH)
• β-Endorphin

I will mostly be expanding on ACTH, CLIP, α-MSH/β-MSH/γ-MSH, and β-Endorphin. These all have a wide range of biological effects.

POMC—both directly and indirectly—is heavily influenced by light (sunlight, artificial light/nnEMFs, biophotons), temperature, hormones (leptin, melatonin, etc.), emotional stimuli (stress, fear, joy, etc.), energy status, and even physical exercise. POMC gets “sliced” into its downstream peptides via the interactions at several amino acid residues.

Blue light-dominant environments seem to cleave POMC into ACTH, CLIP, and γ-lipotropin. To a lesser extent, this also applies to red light too. Ultraviolet-A (UVA) has an influence on α-MSH and β-endorphin. Ultraviolet-B (UVB) has a heavier influence on α-MSH and β-Endorphin. Cold thermogenesis has an effect on a-MSH, ACTH, and β-Endorphin—one of the reasons why Eskimos are so tanned. β-MSH and γ-MSH are also induced by UVA/UVB light, but less research has been done. Let’s dissect this further into each peptide and its effects.

1. Adrenocorticotropic Hormone (ACTH)

POMC cleaving into ACTH via blue light makes a lot of sense when you take into consideration what happens at sunrise. Sunrise contains blue and red light, with an absence of UV light. So this natural rise in ACTH will induce a quantized release of cortisol in the AM, allowing for alertness through the day. You can see how this is problematic in the modern world, where we have constant isolated blue light exposure via LED lighting, tech devices, screens, etc. (especially on top of stress/trauma, which also drives excess ACTH/CLIP).

This natural response will then dampen once UVA light penetrates the atmosphere a few hours after sunrise, which is geared towards other POMC peptides, pituitary hormones, and aromatic amino acid’s downstream products (testosterone, progesterone, thyroid, dopamine, serotonin, etc.) This is also tied to circadian biology and how the dynamic light frequencies of sunlight, as well as darkness, influence our hormonal cycles through the day and night.

ACTH receptors are found on several cell lines—including adrenal cells, various regions of the brain, immune cells, melanocytes, and ovaries/testes. It acts as an allosteric inhibitor of our most valuable POMC peptide, α-MSH—due to its effect on blood glucose and interactions with melanocortin (MC1-5) receptors. ACTH increases both cortisol and aldosterone. It also increases DHEA synthesis due to its counterbalancing effect on cortisol.

2. Corticotropin-like Intermediate Peptide (CLIP)

CLIP activity normally coexists with ACTH. As ACTH influences the fight-or-flight stress response, increasing blood glucose levels, CLIP functions as an insulin secretagogue in the pancreas. This being chronically elevated—alongside ACTH—drives adrenal, leptin, and insulin resistance at various levels.

3. Melanocyte-Stimulating Hormone (α-MSH/β-MSH/γ-MSH)

MSH is found in three forms: alpha, beta, and gamma. α-MSH is cleaved from the middle region of POMC, β-MSH is from the C-terminus, and γ-MSH from the N-terminus. Most research has been done on alpha, so we will start there.

Within the brain—especially the hypothalamus—α-MSH is heavily influenced by leptin signaling, which is directly tied to light, circadian biology, and bioenergetic status in general. This pathway is called the ‘leptin-melanocortin pathway’. Alongside melatonin, leptin is one of our main circadian-influenced hormones—it acts as a fuel gauge of energy (electrons, protons, photons) status. If this pathway is functioning correctly, leptin signaling will be effectively regulated, leading to optimal release of α-MSH and reduced levels of ACTH/cortisol.

α-MSH within various brain regions positively influences appetite, energy homeostasis, dopamine, melatonin, immunity, libido, and more. But α-MSH doesn’t just end there, it also has some cool functions in the periphery.

α-MSH has potent antimicrobial properties, it regulates cholesterol/bile acid metabolism in the liver, influences eNOS/nitric oxide, and also has immunomodulatory effects. 95% of patients with mold/mycotoxin toxicity have low α-MSH levels. a-MSH plays a role in activating the anti-inflammatory cholinergic pathway, converting effector T cells into T regulatory cells, inhibiting NF-kB activation induced by TLR ligands, and regulating the release of various cytokines.

α-MSH is also the main driver of melanogenesis via MC1 receptor activation, which increases melanocyte proliferation, as well as melanosome/melanin production. Melanin is an EXTREMELY important molecule to have at optimal levels in the modern world—it is a semiconductor, redox controller, heavy metal/toxin chelator, ties in with mitochondria/bioenergetics, and much more.

Collectively—melanin/α-MSH is a swiss army knife: Bioenergetics, semiconductor, antioxidant, chelates heavy metals/toxins/ions, emits/absorbs light/biophotons, regulates appetite/hormones, anti-inflammatory, antifungal, controls magnetochemistry, induces libido, protects DNA, breaks down into other tyrosine-derived neurotransmitters/hormones, and depletes deuterium.

You can find a deep dive on melanin/α-MSH research here.

Touching on the less researched β-MSH/γ-MSH. β-MSH is derived from β-lipotropin and acts as an agonist of MC4 receptor, which modulates pain, immunity, and appetite. γ-MSH acts as a partial agonist of MC1 receptor and acts as a regulator of melanogenesis.

4. β-endorphin

And, of course, we have β-endorphin—our most powerful endogenous opiate. It acts as a potent mu-opioid receptor (MOPr) agonist (magnesium/Mg2+ required), which is involved in pain modulation and pleasure/reward and overall influences dopaminergic activity within the striatum. This reinforces us to be addicted to sunlight and anything else that induces a natural endorphin response. Sunlight also increases dopamine, serotonin, and endocannabinoids, which also enhance our mood.

One of many examples: β-endorphins are found low in patients with PTSD, as well as high ACTH/cortisol. It is also associated with OCD, anxiety, depression, addiction, and more neurological disorders. POMC cleavage is key to optimizing neurochemistry and your biology in general.

Physical exercise influences POMC expression beyond just β-Endorphin:

Exercise not only induces B-endorphin but also enhances the whole POMC system through signals via our mitochondria. Influencing mood, appetite, energy expenditure, fat burning, thermogenesis, and other important things downstream.

5. POMC optimization

All forms of stress (light/environmental, mental, metabolic) hijack POMC biology away from α-MSH /β-Endorphin and more towards ACTH/CLIP. Chronic ACTH stimulation tanks DHEA status and also inhibits sex hormone synthesis (testosterone, estrogen, progesterone) at various levels. Low α-MSH leads to impaired sexual function, immune control, appetite dysregulation, and low melanin stores (semiconductor, bioenergetics, ion chelation/control, purine/pteridine control, catecholamine/thyroid reservoir). Low β-Endorphin leads to addictive behaviors towards artificial substances that are associated with opioidergic, dopaminergic, GABAergic, and cannabinoidergic pathways in the nervous system. Native EMFs (sunlight, earth’s magnetic field, Schumann’s, etc.) cleave POMC biology more towards α-MSH/β-Endorphin, whereas non-native EMFs (artificial light, tech devices, Bluetooth, etc.) are geared towards ACTH/CLIP.

How to optimize POMC biology:

1. Ensure light-dark cycles are on-point and tuned to nature: lots of sunlight throughout the day on skin/eyes, limit blue light/nnEMFs, and use red/candlelight at night.
2. Touching deeper on sunlight: make sure you’re outside for the various phases of sunlight (sunrise, UVA, UVA/UVB, sunset, darkness).
3. Expose yourself to your environment: grounding, nature, hot, cold, etc. This is especially important for the cold/winter months.
4. Address any stress/trauma to ensure POMC cleavage isn’t geared towards excess ACTH/CLIP.
5. Seasonal nutrition, with emphasis on cofactors for POMC-related enzymes: vitamin C, zinc, glycine, copper, calcium, and vitamin B5.
6. Address all fundamental health components: mindset, breathing, hydration, sleep, light, movement, nutrition, and connection.