Hi girls,
Sorry I'm a bit late, but here goes. Sentences in bold are mine.
Necessary background:
1 g = 1,000 mg = 100,000 µg = 100,000,000 ng = 1,000,000,000 pg.
‘17β‐estradiol' has been substituted by estradiol in the main text. Greek letters have been substituted by alpha, beta and gamma or left out when not needed. '5α‐DHT' has been substituted by DHT.
The purposes of this review:
‘(a) the hair follicle in mammals vs humans for growth and cycle control;
(b) the 5α‐reductase enzyme and the impact of 5α‐dihydrotestosterone (5α‐DHT) on the human hair follicle;
(c) steroids, in general, and estrogens specifically (ie,17β‐estradiol) on their influence of the human hair follicle that may be inhibitory or stimulatory;
(d) estrogen receptors (ER) alpha (α) and beta (β), G protein‐coupled estrogen receptors (GPR30 or GPER), and even the orphan receptor, estrogen‐related receptor (ERR) gamma (γ), as potential mediators of estrogen hormone actions in hair follicles; and
(e) steroidogenesis by aromatase and 5α‐reductase expression and their enzyme activities.
Hair follicle is a dynamic mini-organ influenced by multiple factors:
‘(…) numerous growth factors, immune molecules, neuropeptides, inflammatory molecules, and hormones.'
Some in vitro studies have used fetal calf serum containing steroids… but recent studies have addressed this issue by substituting it.
Estradiol and progesterone dose response show inverted U-shape curves, meaning more is not necessarily better, intermediate doses may be more effective:
‘(…) 1 nmol/L of progesterone inhibited DHT synthesis by 75% and 100 nmol/L and 1 µmol/L levels of progesterone inhibited DHT formation by 99% and 96%, respectively.
The intermediate estrogen dose of 10 nmol/L appeared to be the most effective in stimulating hair shaft elongation from the Conrad report. This dose.response inverted U-shape curve has been reported for estrogen effects in brain activity (hippocampal neurons) in young women where physiological estradiol concentrations stimulate brain activity, whereas supraphysiological estradiol ranges (as seen during pregnancy) display inhibitory effects. Such findings may not be surprising since the overall “tone†of the brain and heart is inhibitory in order to maintain homeostasis.
Additionally, in the report by Conrad et al they showed that hair shaft elongation was significantly stimulated by 1‐100 nmol/L estradiol from a healthy man. Notably, from this report, the 1 nmol/L and 100 nmol/L estradiol results were very similar, while the 10 nmol/L level of estradiol displayed the greatest stimulatory effect on hair shaft elongation.'
Scalp hair follicles respond differently from body hair follicles.
Human hair follicles respond differently from other mammals hair follicles.
‘Much of our understanding of hair biology has been based upon research in rodents since human and murine hair follicles share similar organizational (cellular) and functional components in the repetitive cycling of the anagen, catagen, and telogen phases.
Early reports from mammals suggested that estrogens (estradiol) usually inhibited hair follicle growth.
Conrad et al. addressed this perplexing topic citing human data for both the inhibition and stimulation of hair growth by estradiol.
However, Oh et al in 2016 noted that while both human and murine hair follicles are very responsive to hormonal stimulation via estrogens and prolactin, these hormones inhibited murine hair follicle growth and cycling, conversely, both hormones prolonged the anagen phase in human female temporofrontal scalp hair follicles.'
Conclusions:
‘Much more is known about the expression and molecular mechanisms of the human estrogen receptors (ER alpha and ER beta) in the hair follicle, which have revealed:
(a) differential expression of ERs from the vertex and occipital scalp in humans,
(b) the distribution pattern of ER beta and TGF-beta 2 (a negative hair growth modulator) is different between males and females and there are substantial sex-dependent differences in the response in fronto-temporal human scalp hair follicles to estradiol,
(c) from murine studies,ER alpha vs ER beta have selective roles in the complexity of hair growth and regulating the hair cycle, and
(d) hormonal activation via dexamethasone in human hair follicles significantly reduced ER alpha expression by 38%, while ER beta levels were unaffected.
Oestrogen, Progesterone & Testostesterone actions on hair follicle are intertwined depending on affinity for receptors and enzymes
'The inhibitory actions of androgens on hair follicle cycling are undisputed, where DHT is more potent than the principal circulating androgen, testosterone, due to its greater affinity (2.5‐5 times) and stability for androgen receptors.
They found that 1 nmol/L of progesterone inhibited DHT synthesis by 75% and 100 nmol/L and 1 µmol/L levels of progesterone inhibited DHT formation by 99% and 96%, respectively.
This "inhibition"of DHT may be misleading since it is known, in general, that the 5 alpha-reductase enzyme has a higher affinity for progesterone as a substrate compared to testosterone, thus possibly reflecting more conversion to 5 alpha-progesterone compared to DHT among the progesterone levels tested.
Kondo et al showed that the growth curves of human scalp hair follicles in organ culture were inhibited by the addition of testosterone or estradiol.
Nelson showed that estradiol inhibits female scalp hair shaft elongation along with the phytochemical, genistein, which selectively binds ER beta.
(…) in human skin and scalp tissue, the expression levels of aromatase and steroidogenic acute regulatory protein (StAR) were positively correlated with estrogens and testosterone concentrations respectively. StAR has been demonstrated to play an important role in the production of steroid hormones by the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane in steroidogenic tissue sites.'
Hormones, Pregnancy & Hair
‘The stimulatory action of estrogens during pregnancy on hair growth has shown that after parturition, the follicles enter the resting phase with associated hair shedding and thinning. However, there is a dramatic decline in progesterone and estrogen levels by approximately 98% (with the delivery of the placenta). This may result in estrogen dominance due to the ng/mL vs pg/mL declination of progesterone and estradiol, respectively, along with the fact that estradiol is the more potent hormone. Also, the rapid decline of progesterone may alter DHT formation since progesterone is a preferred substrate for the 5 alpha-reductase enzyme that could alter the estrogen/androgen ratio resulting in hair shedding and thinning after parturition.'
Other factors influence hair follicle:
Dexamethasone and other steroids
‘Additionally, dexamethasone treatment stimulated the expression of aromatase mRNA levels by ninefold with a corresponding increase in aromatase activity in both frontal scalp and beard hair follicles. These reports suggest selective estradiol and other hormone actions via ERs that may involve systemic and/or locally synthesized steroid hormone, or other signaling mechanisms that remain to be elucidated.
Other oestrogen receptors
Finally, the discovery in human skin of the orphan receptor that is a member of the nuclear receptor superfamily, namely estrogen related receptor gamma (ERR gamma) displays strong sequence homology estradiol with ER alpha but does not bind estradiol and information on GPR30 or GPER in hair follicles is lacking especially in light of the well.known beneficial effects this receptor has in inhibiting breast cancer.
Enzyme levels variability
'More recently, Sanchez et al showed that aromatase mRNA levels in plucked hair follicles were significantly lower in women with female pattern hair loss (FPHL). Additionally, the mRNA levels of all three 5 alpha-reductase enzymes were increased in some women with FPHL, but not in others, which may explain the lack of effectiveness of 5 alpha-reductase inhibitors in some FPHL women.'
Dietary soy isoflavones
‘The dietary derived polyphenol, equol, is present in the circulation of humans at various concentrations regardless of age, race, gender, or geographical location in the world. In this case, equol is a selective ER beta agonist, is known to bind ERR gamma which it is thought to protect against neoplastic growth. Other phytochemicals such as genistein have been shown to alter human scalp hair shaft elongation.
Estrone
‘Substantial rates of estrogen formation from estrone sulfate (via steroid sulfatase) were found in anagen hair follicles where estrone accounted for 97% and estradiol 3% of the formed estrogens. A selective decrease in estradiol was observed in telogen compared to anagen hair follicles suggesting an impaired formation of estradiol in the presence of high estrone levels. The authors concluded that the resulting loss of estradiol may cause the transformation from anagen to telogen hair, since the principal hormone action of estradiol is to prolong the anagen phase of human scalp hair and to decrease the length of the telogen phase.'
The bulletproof reality:
‘It is still rather unclear what exactly estradiol administration does to human scalp hair growth.'
“It is no longer justifiable to portray telogen as the resting stage of the human follicle cycle…. It is a master switch stage in the control of human follicle cyclingâ€.'
BeaR.