main target for hairloss : hormonal pathway

[Shinobi]

Hello guys,

I came aware a study wich clearly explain what we discussed with CS regarding ERb as main target for hair. Here is the answer i think we all have to know, this is in human study, so there is no speculation on mice on other kind of cells here:

"The results of this immunohistochemical study propose that estrogen receptor beta and not estrogen receptor alpha is the main mediator of estrogen action in human skin and the hair follicle. Further studies with androgen-dependent skin are required to determine whether estrogen receptor beta has a regulatory role on androgen receptor expression in the hair follicle in parallel with its role in other androgen-dependent tissues."

and:

"ERbeta was the predominant steroid receptor in both male and female human nonbalding scalp skin. In the hair follicle, ERbeta was immunolocalized to the cell nuclei of the outer root sheath, epithelial matrix, and dermal papilla cells (seeFigure 2). This was in contrast to ERalpha, which did not stain the hair follicle cells, and AR, which only stained dermal papilla cells. Serial sections of one follicle clearly showed ERbeta strongly expressed in the bulge, whereas there was no staining for either ERalpha or AR. ERbeta was also expressed in the nuclei and cell membranes of the partially differentiated sebocytes"

and:

"The results of the present immunohistochemical study demonstrate that ERbeta and not ERalpha is the main mediator of estrogen action in human skin and the hair follicle. "

"By extension, an important role for ERbeta in the human hair follicle may be to regulate androgen-dependent hair growth by modulating AR expression or androgen signaling pathways. In this respect, it is noteworthy that finasteride, an inhibitor of 5alpha-reductase, has only been shown to be effective in men and not postmenopausal women to treat androgenetic alopecia "

We should also consider one thing in parallel, its already known but still very important:

"Also other recent studies byLachgar et al (1999) have shown that finasteride upregulates aromatase expression in cultured scalp dermal papilla cells, indicating that finasteride might have an estrogen promoting effect because it increases the amount of testosterone that is converted to 17beta-estradiol (Figure 1). Furthermore,Sawaya (2000) has reported that there are differences in aromatase expression in scalp follicles taken from men and women and also between occipital and frontal follicles. That study showed higher levels of aromatase activity in occipital scalp follicles compared with frontal scalp follicles in both sexes; however, aromatase activity was 6-fold higher in frontal hair follicles of females compared with males."

aromatase convert androgen to estrogen (conversion of testosterone to 17beta-estradiol and androstendione to estrone)

DHT stimulate aromatase in other king of tissue, conflicting a bit the picture:

Stimulation of aromatase activity by dihydrotestosterone in human skin fibroblasts.
Chabab A, Sultan C, Fenart O, Descomps B.
Abstract
In order to study the regulation of aromatase activity by androgens in cultured fibroblasts derived from genital skin of normal prepubertal boys, aromatase activity was evaluated in the presence of various concentrations of non-aromatizable androgen DHT(5 alpha-dihydrotestosterone). The estrogen formation was assayed by an enzymatic method, after 24 h incubation of the cells with 10(-6) M androstenedione. Aromatase activity was stimulated 3- to 20-fold by DHT at concentrations 10(-10) and 10(-9) M. It was necessary to preincubate the cells with DHT for 48 h in order to bring about this stimulation. The stimulatory effect was not significant after preincubation for only 24 h. The basal value of aromatase activity was in the range of 8 +/- 1.2 pmol/mg protein/day (mean +/- SEM), while the maximal stimulation 1043 +/- 46 pmol/mg protein/day was obtained at the concentration of 10(-Cool M DHT. This stimulation was partially blocked with cyproterone acetate at level of 20 +/- 4 pmol/mg protein/day; stimulation of aromatase activity by DHT could thus be mediated by the androgen receptor. This stimulatory effect was prevented by incubation of the cells with cycloheximide or actinomycin D, suggesting that DHT acts to increase aromatase activity in cultured fibroblasts by inducing the synthesis of new proteinaceous material. In vitro regulation of aromatase activity by androgens could contribute to a new approach to the extraglandular formation of estrogen.

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Interestingly, the expression of aromatase in human genital skin fibroblasts has been shown to be androgen dependent, with much lower levels of expression in cells from patients with androgen insensitivity syndromes (Stillman et al, 1990). In addition, androgens can significantly increase aromatase activity in cultured genital skin fibroblasts, which can be blocked by an anti-androgen (Stillman et al, 1991), demonstrating that the response is mediated via the AR.

Come back to aromatase and hair loss:

Aromatase inhibitor therapy and hair loss among breast cancer survivors.
Gallicchio L1, Calhoun C, Helzlsouer KJ.
Author information
Abstract
The objective of this study was to examine the associations between aromatase inhibitor therapy and hair loss or hair thinning among female breast cancer survivors. Data were analyzed from 851 female breast cancer survivors who responded to a hospital registry-based survey. Data on hair loss, hair thinning, demographic characteristics, and health habits were based on self-report; data on aromatase inhibitor therapy were collected on the survey and verified using medical record review. Logistic regression was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between aromatase inhibitor therapy and the hair outcome variables adjusted for potential confounders, including age and chemotherapy treatment. The results showed that 22.4 % of the breast cancer survivors reported hair loss and 31.8 % reported hair thinning. In the confounder-adjusted analyses, breast cancer survivors who were within 2 years of starting aromatase inhibitor treatment at the time of survey completion were approximately two and a half times more likely to report reporting hair loss (OR 2.55; 95 % CI 1.19-5.45) or hair thinning (OR 2.33; 95 % CI 1.10-4.93) within the past 4 weeks compared to those who were never treated with an aromatase inhibitor. Current aromatase inhibitor use for two or more years at the time of the survey and prior use were significantly associated with hair thinning (current users, ≥2 years: OR 1.86; prior users: OR 1.62), but not hair loss. Findings from this study suggest that aromatase inhibitor use is associated with an increased risk of hair loss and hair thinning independent of chemotherapy and age; these side effects are likely due to the substantial decrease in estrogen concentrations resulting from treatment with this drug. Future research should focus on examining these associations in a prospective manner using more detailed and objective measures of hair loss and thinning.

So we know why natural 5AR inhibitor doesnt do much, because they often also decrease aromatase.

Crazy thing is resveratrol is a potent aromatase inhibitor:

Resveratrol concentration of 20 μM have an aromatase inhibitory effect as potent as 20 nM letrozole, which is a clinically used anti-aromatase drug in breast cancer treatment. http://www.sciencedirect.com/science...87233314001040



We really should found a way to increase aromatase in scalp (since its not healthy for the body) and target ERb in order to decrease 5AR and reverse hairloss

[Gjm127]

I've been taking Resveratrol pills every morning for the past 2 years. At first I thought it helped, but now it seems as though it's not really. Should I stop using it? I'm mainly doing it for hairloss.

[Shinobi]

I've been taking Resveratrol pills every morning for the past 2 years. At first I thought it helped, but now it seems as though it's not really. Should I stop using it? I'm mainly doing it for hairloss.

We cant clearly reply this question because 2 things:

1/ resveratrol decrease aromatase but also 5AR, so there is a balance benefit / loss

2/ resveratrol decrease aromatase in breast cancer, doesnt mean it does same in scalp.

For now its hard to say if its good for hair or not.