@bridgeburn ,
@Wolf Pack ,
@itchymadscalp ,
@AnxiousAndy ; I got this artical
https://academic.oup.com/edrv/article/27/6/677/2355194 over the Internet. This explains the effect of Estrogen on hair follicles. I have problem in understanding the whole artical. Can you explain it to me?
Its too complicated for me to understand completely and alot to explain cause its super long. but basically a few things it says is that
-hair is a source of estrogen. and also has receptors for it.
- E modulates growth phases.
- it also affects androgen metabolism with a few indirect effects.
-It acts on different kinds of estrogen receptors; ie. ER alpha and Beta receptors.
-because of that it has a different effect of mice, animals, etc. than in humans
-17-b estradiol stimulates VEGF, (something minoxidil also stimulates hair with)
- Hair is affected immune system, mast cell activation switches terminal hair towards miniaturization
-estradiol is an immunomodulator, but its still speculative if this is relevant in controlling hair cycle
- "Although hair growth disorders like hair loss and hirsutism are often trivialized, they can profoundly affect a patient’s quality of life (82)."
its good they admit this. It then goes on to say basically, "why aren't we studying this more??" "why aren't we selling something based on estrogenic research?"
- the paper then states that most reasons for hair loss is a problem with hair cycling and only a minority have a problem with actual hair shaft production.
"Even the dramatic skin appendage transformations that remodel a large terminal hair follicle into a tiny vellus hair follicle are now recognized to be hair cycle-dependent phenomena"
maybe people who have the worse problem won't respond to anything?
- "hair follicle cycling begins with catagen, not with the actual growth phase, anagen."
that's probably why its normal to shed at the beginning, and why we should wait a few months before claiming something doesn't work.
- I guess there's another way for T to become E besides aromatase?
" testosterone is converted to 19-hydroxytestosterone by a monooxygenase (EC 1.14.13.), then to 19-oxotestosterone, which is then converted to E2 by an oxidoreductase (EC 1.14.99.)."
- In males, "About 60% of circulating E2 is thought to arise from peripheral aromatization of testosterone, whereas 20% is formed by reduction of estrone"
- hair follicles are known to contain aromatase
-The effect of estrogens depends on the subtype recepter, ERa ERb
" It is known that ERα and ERβ regulate some gene promoters with AP-1 sites in an opposite manner "
- apparently its possible that ERs can be activated by growth factors without estrogen after they are produced, however, in certain cells they are increased by estrogen itself.
"Growth factors such as IGF-I, EGF, and TGFα, through activation of MAPK pathway, regulate phosphorylation of ER influencing its transcriptional activity. Also, in the absence of estrogen, ER can be activated by these growth factors (184). Moreover, in different cell types, estrogen regulates the expression of EGF, IGF-I, and TGFα, suggesting that these growth factors are mediators of estrogen action (181). "
"Thus, given the well-appreciated central role of IGF-I, EGF, and TGFα in hair follicle biology, the cross talk between peptide growth factors and ER signaling pathways may be highly relevant in hair growth control."
- estrogen receptors are found in many organs and cell types
- the receptors can change in mutated cancer cells
ERb --> ERbcx
- ERb sounds like its the more predominant estrogen receptor in the human hair follicle than ERa.. (ERa is bad for hair, ERb is good for hair)
"ERα was poorly expressed, being restricted to sebocytes. In contrast, ERβ was highly expressed in the epidermis, sebaceous glands (basal cells and sebocytes), and exocrine sweat glands.
In the hair follicle, ERβ is widely expressed with strong nuclear staining in dermal papilla cells, inner sheath cells, matrix cells, and outer sheath cells including the bulge region."
This bold part worries me:
" In the hair follicle, ERβ expression was localized to nuclei of outer root sheath, epithelial matrix, and dermal papilla cells,
in contrast to ERα, which was most prominently expressed in dermal papilla cells. "
later it says this:
"Thus, because both androgen receptor and ERβ are prominently expressed in the hair follicle [
i.e., in follicular dermal papilla cells"
But it sounds better here:
"Serial sections also showed strong nuclear expression of ERβ in the cells of the bulge,
whereas ERα was not expressed. In the sebaceous gland, ERβ was expressed in both basal and partially differentiated sebocytes. ERα exhibited a similar pattern of expression. "
- The majority of estrogens effects are mediated from ERa and ERb.
-Different types of tissues have a different predominant receptor. ie, ERa: pituitary, uterus, boob. ERb: lung, prostate, skin
- "there are numerous reports demonstrating that estrogen and androgen metabolites can interact with both receptor subtypes"
- Of all hormones that decline with age, estrogens apparently have the most dramatic effect on the skin (215), and this occurs in more than one way.
- Estrogens dampen inflammation
- It inhibits oxidative stress in hair (through bcl-2)
- Ok, now maybe ERa is not so bad??
"Other authors have suggested that estradiol effects on keratinocytes are mediated via a membrane ERα that activates the MAPK pathway."
- Estrogen needs stem cells to work
"ERβ is strongly expressed in the bulge region of the outer root sheath. This region contains stem cells for hair follicle keratinocytes that regenerate the follicle during the anagen phase. This suggests that these epithelial stem cells are targets for estrogen action."
hmmm, maybe people should dermaroll before taking HRT?
- "..estrogens play an important role in the maintenance and the regulation of the hair follicle "
- The hair on the back of the head has ER expression locked in the ON position. Even If we are not currently bald, hair on the top is more venerable.
"it was reported that in cultured dermal papilla cells from nonbalding male donors, both ERα and ERβ showed a consistently higher expression, both at the RNA and protein levels, in occiput dermal papilla cells compared with vertex dermal papilla cells (258). "
- females have better frontotemporal ERb expression than males
- Estradiol reduces PGD2
- estrogen, along with androgens helps stimulate some pubic hair
- estardiol slows down hair growth but keeps it in the anagen phase longer except for the frontotemporal follicles in men where it sped up growth and increased anagen.
- ERb expression was in different locations of the follicle unit in male and female frontal follicles.
-the slowed hair growth isn't enough to be noticeable without fancy machines
- "Estrogens have been used for topical treatment of hair diseases for more than half a century"
- "Some studies have reported an increased anagen and decreased telogen rate after treatment with estrogens, compared with placebo"
- estrogens are commercially available in Europe for women with hairloss
- " Due to unwanted side effects like gynecomastia, E2 should not be used in men because very high topical doses seem to be required to obtain measurable hair growth effects "
haha
- a weaker version of estradiol; 17-alpha estradiol is sometimes prescribed for men
- It continues to stress that there needs to be properly done clinical trials and research but nobody gives a sh*t about us baldies
- estradiol upregulates progesterone receptor
- it upregulates many genes involved in follicle signalling
- It increases cyclin d1 through MAPK pathway, but that effect of E can be countered by a MAPK inhibitor
- theres possible crosstalk between estradiol/ ER with melatonin and prolactin.
- ERa may attenuate prolactin receptor in vitro
- melatonin downregulates ERa expression
(in mouse skin)
- "Like estrogens, cortisol can even be synthesized in the hair follicle itself, where it stimulates glucocorticoid receptors (52)."
