Estrogen Darkens Skin Color, Progesterone Lightens It

[haidut]

It has been known since ancient Greek times that during pregnancy skin color in women changes drastically. Doctors have long suspected that hormones are involved but until now the mechanism was not known. This study shows that estrogen and progesterone are involved in skin color changes. Estrogen increases the production of melanocytes and causes skin to darken, while progesterone works in the opposite direction and lightens skin color. While it would be premature to say that estrogen directly causes melanoma (even though I suspect it) the increased and uncontrolled production of melanocytes is a necessary condition for melanoma to develop and it seems that estrogen is a primary driver of that process, while progesterone opposes it. I posted another study recently showing that pregnenolone is another hormone that may be effective in stopping melanoma progression directly and its conversion into progesterone is likely to have additive beneficial effect.
Pregnenolone For Protection Against Melanoma
Peat also wrote in one of his articles how he made his "active melanomas" disappear by rubbing progesterone and DHEA on them and this study seems to back up his approach.

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors. - PubMed - NCBI
Penn Medicine study uncovers new pathways that control skin tanning and lightening | Science Codex
Scientists Find New Way to Tan or Lighten Skin

"...Researchers found that skin color can be regulated by estrogen and progesterone, two of the main female sex hormones. Estrogen darkens the skin; progesterone lightens the skin. Although this much was known to a limited degree, the new research revealed two cellular receptors that appear to control this process in skin cells called melanocytes."

"...By studying human skin cells both in a petri dish and in a 3D-bioengineered patch of skin about the size of a postage stamp, Ridky's team discovered a different, unexpected set of receptors on melanocytes that do interact with the sex hormones. Specifically, they found a receptor called GPER that interacts with estrogen and triggers melanin production, and a receptor called PAQR7 that interacts with progesterone and decreases melanin production."

 

[Ewelina]

Interesting, thanks Haidut!

 

[PowertothePeatple]

Addison's causes skin darkening too. Is that related mechanism? Maybe commonality of stressed metabolism.

 

[haidut]

Addison's causes skin darkening too. Is that related mechanism? Maybe commonality of stressed metabolism.

That is actually a very good point. While the hyperpigmentation observed in Addison disease is believed to be due to elevated ACTH, I think estrogen may be involved as well since ACTH is one of the most potent inducers/activators of aromatase.
Regulation of aromatase activity of cultured adipose stromal cells by catecholamines and adrenocorticotropin. - PubMed - NCBI

Thus, high ACTH would generally mean high tissue levels of estrogen. It would be interesting to see results from people with Addison's who also take aromatase inhibitors. If their skin does not darken then we can conclude estrogen is the actual cuplrit in the hyperpigmentation of Addison disease. Unfortunately, most clinicians don't know enough about the HPA axis to even make that connection despite the fact that Addison patients have classic symptoms of estrogen excess such as weight gain, puffiness, edema, etc.

 

[lindsay]

Very interesting! Thank you for sharing!!

I was speaking with a dermatologist last weekend while working at a wedding, and he specializes in melanoma research (in DC actually) - our dog has dermatitis, so I was telling him about his skin problems and the quasi-immunosuppressant we have him on (it's the only thing we've found to work so far). He said that people who take immunosuppressants are more prone to melanoma and that it's one of the things they check for - why might this be?

 

[Diokine]

Interesting topic, Dr. Peat has talked about the bioenergetic implications of skin pigment, as melanin is an electron shuttle and is intimately involved in redox reactions. It is typically produced by exposure to UV radiation, and the estrogen link is important because proper estrogen signaling is required for protection against UV exposure.

I think it's a perfect example of the "interaction between an organism and it's environment," particularly as it relates to perceived stress and appropriate reaction to said stress. UV light exposure can generate a lot of free radicals and other reactive species, and melanin is required to manage and offset these. It stands to reason that this mechanism of protection can be applied to other forms of stress, not just that caused by UV radiation.

 

[tyw]

Interesting topic, Dr. Peat has talked about the bioenergetic implications of skin pigment, as melanin is an electron shuttle and is intimately involved in redox reactions. It is typically produced by exposure to UV radiation, and the estrogen link is important because proper estrogen signaling is required for protection against UV exposure.

I think it's a perfect example of the "interaction between an organism and it's environment," particularly as it relates to perceived stress and appropriate reaction to said stress. UV light exposure can generate a lot of free radicals and other reactive species, and melanin is required to manage and offset these. It stands to reason that this mechanism of protection can be applied to other forms of stress, not just that caused by UV radiation.

Agree. The marker used by the researchers in the first study was GPER (G protein-coupled estrogen receptor 1). This is just a protein, that seems to be "activated by estrogen", but also by many other compounds.

Sidenote: just search for "G protein-coupled receptors", and you'll find a whole host of inputs, ranging from eating PUFAs to Circadian Cycle disruption.​

Proteins really are just electromagnetically activated and de-activated by various stimuli. Compounds like estrogen can do it, but so too would many, many other things.

This is also why Peat said something like "the cell chooses which hormones to use" (Generative Energy Podcast #26) -- #26: Talking with Ray Peat #2: Carbon Dioxide, NAD+/NADH, Antibiotics, Coffee .

This makes sense, since hormones and other compounds would just be encoders of varying quantas of energy. The transfer / deduction of energy from specific compounds on a cell membrane is the very definition of "receptor signalling".

....

 

[dookie]

@haidut , et al.

When I use progesterone, I notice that my skin color actually looks a bit more "tan" or darker. Coffee seems to do the same. Orange juice on the other hand makes me look more "white". Any thoughts? Could the increased tan look be from improved blood circulation to the skin?

 

[Parsifal]

Would it have something to do with elevated copper (oestrogen precursor) and ceruloplasmin?

 

[Koveras]

It has been known since ancient Greek times that during pregnancy skin color in women changes drastically. Doctors have long suspected that hormones are involved but until now the mechanism was not known. This study shows that estrogen and progesterone are involved in skin color changes. Estrogen increases the production of melanocytes and causes skin to darken, while progesterone works in the opposite direction and lightens skin color. While it would be premature to say that estrogen directly causes melanoma (even though I suspect it) the increased and uncontrolled production of melanocytes is a necessary condition for melanoma to develop and it seems that estrogen is a primary driver of that process, while progesterone opposes it. I posted another study recently showing that pregnenolone is another hormone that may be effective in stopping melanoma progression directly and its conversion into progesterone is likely to have additive beneficial effect.
Pregnenolone For Protection Against Melanoma
Peat also wrote in one of his articles how he made his "active melanomas" disappear by rubbing progesterone and DHEA on them and this study seems to back up his approach.

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors. - PubMed - NCBI
Penn Medicine study uncovers new pathways that control skin tanning and lightening | Science Codex
Scientists Find New Way to Tan or Lighten Skin

"...Researchers found that skin color can be regulated by estrogen and progesterone, two of the main female sex hormones. Estrogen darkens the skin; progesterone lightens the skin. Although this much was known to a limited degree, the new research revealed two cellular receptors that appear to control this process in skin cells called melanocytes."

"...By studying human skin cells both in a petri dish and in a 3D-bioengineered patch of skin about the size of a postage stamp, Ridky's team discovered a different, unexpected set of receptors on melanocytes that do interact with the sex hormones. Specifically, they found a receptor called GPER that interacts with estrogen and triggers melanin production, and a receptor called PAQR7 that interacts with progesterone and decreases melanin production."

It seems exogenous melanin activates various inflammatory pathways (NFkB and TLR4)

Possible relationship with skin darkening effect of estrogen and lightening effect of progesterone?

Herbal melanin activates TLR4/NF-kappaB signaling pathway. - PubMed - NCBI
Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4). - PubMed - NCBI
Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. - PubMed - NCBI
Nigella sativa seed extract and its bioactive compound thymoquinone: the new melanogens causing hyperpigmentation in the wall lizard melanophores. - PubMed - NCBI

 

[haidut]

It seems exogenous melanin activates various inflammatory pathways (NFkB and TLR4)

Possible relationship with skin darkening effect of estrogen and lightening effect of progesterone?

Herbal melanin activates TLR4/NF-kappaB signaling pathway. - PubMed - NCBI
Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4). - PubMed - NCBI
Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. - PubMed - NCBI
Nigella sativa seed extract and its bioactive compound thymoquinone: the new melanogens causing hyperpigmentation in the wall lizard melanophores. - PubMed - NCBI

Very likely. Progesterone antagonizes TLR4 and inhibits release of NF-kB (due to LR4 or other pathways like COX/LOX).

 

[LeeLemonoil]

What do you think, is endogenous Melanin production a protective response to inflammation or tissue-damage caused by radiation, estrogens etc. or is it in itself
a destructive process?

Also, Thymoquinone seems to offer promisinf properties, could it be a "Peat approved" Quinone/Phytochemical?
Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. - PubMed - NCBI

 

[haidut]

What do you think, is endogenous Melanin production a protective response to inflammation or tissue-damage caused by radiation, estrogens etc. or is it in itself
a destructive process?

Also, Thymoquinone seems to offer promisinf properties, could it be a "Peat approved" Quinone/Phytochemical?
Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. - PubMed - NCBI

Melanin synthesis can be triggered by both ACTH and DHEA. So, it really depends. Initially, if there is enough DHEA synthesis the melanin synthesis is probably a indication of processes. But if ACTH runs unopposes and DHEA declines with age, eventually this melanin accumulation can become pathological.
Dehydroepiandrosterone inhibits B16 mouse melanoma cell growth by induction of differentiation. - PubMed - NCBI

 

[lvysaur]

This could also be due to the heat labile nature of tyrosine. If progesterone increases body heat, then tyrosine breaks down and less melanin.

I also have a suspicion that adrenergics darken color. Wilds are darker than domestics, old darker than youth, and men darker than women.

 

[pimpnamedraypeat]

Is this why people in sunnier climates are more volatile and emotional?

I'm thinking of a specific summer I spent in florida and it seemed like everyone was off their rocker across all social, cultural, religious, or racial boundaries.

Sun exposure increases production of melanin thereby increasing estrogen in the process

 

[Herbie]

Is this why people in sunnier climates are more volatile and emotional?

I'm thinking of a specific summer I spent in florida and it seemed like everyone was off their rocker across all social, cultural, religious, or racial boundaries.

Sun exposure increases production of melanin thereby increasing estrogen in the process

The humidity in Florida might also contribute. Peat has said that its a slight stress to the system.

In Australia in the northern areas above the tropic of capricorn, its hot and humid on the coast where most people live and when people go mad/crazy the people call it going tropo.

 

[pimpnamedraypeat]

The humidity in Florida might also contribute. Peat has said that its a slight stress to the system.

In Australia in the northern areas above the tropic of capricorn, its hot and humid on the coast where most people live and when people go mad/crazy the people call it going tropo.

Ha! Going tropical that's funny

 

[noordinary]

It has been known since ancient Greek times that during pregnancy skin color in women changes drastically. Doctors have long suspected that hormones are involved but until now the mechanism was not known. This study shows that estrogen and progesterone are involved in skin color changes. Estrogen increases the production of melanocytes and causes skin to darken, while progesterone works in the opposite direction and lightens skin color.

@haidut does that mean that Linea nigra (that used to be not that common just a century ago, and now is considered "normality" for any pregnancy) may be caused by high estrogen to progesterone ratio? Current medical position is that Linea nigra is caused due to increased MSH (melanocyte-stimulating hormone) produced by placenta.
Also darkening of the labium and anus is associated with pregnancy and aging. Anus bleaching (no joke) gets more and more popular. Beauty industry is always after what youthful high energy state is all about, lighter colored anus in that case.

 

[lvysaur]

Is this why people in sunnier climates are more volatile and emotional?

In my experience, it seems like whites are more volatile/emotional than northern or southern Asians (Japs or Thais), both of which get more insolation. But your mileage may vary.

People commit more crime during the hotter months, but it's unclear whether that's due to sun, heat, or just ease of crime.

 

[haidut]

@haidut does that mean that Linea nigra (that used to be not that common just a century ago, and now is considered "normality" for any pregnancy) may be caused by high estrogen to progesterone ratio? Current medical position is that Linea nigra is caused due to increased MSH (melanocyte-stimulating hormone) produced by placenta.
Also darkening of the labium and anus is associated with pregnancy and aging. Anus bleaching (no joke) gets more and more popular. Beauty industry is always after what youthful high energy state is all about, lighter colored anus in that case.

Quite possibly yes, as estrogen and ACTH (both increase in aging) are known stimulants of MSH release.

The influence of hormones on melanogenesis. - PubMed - NCBI
Melanocyte-stimulating hormone - Wikipedia
"...An increase in MSH will cause darker skin in humans too. MSH increases in humans during pregnancy. This, along with increased estrogens, causes increased pigmentation in pregnant women. Cushing's disease due to excess adrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. Most people with primary Addison's disease have darkening (hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule, proopiomelanocortin (POMC)."