NEW TOPICAL DRUG TO REGROW HAIR

[thatdguy]

Has anyone ever heard of this?
http://www.bio-medicine.org/medicine-ne ... s--2696-1/

Adult hair follicles undergo a growth cycle consisting of periods of growth (anagen), regression (catagen), and rest (telogen). Researchers demonstrated that the brief activation of ?-catenin in // telogen-phase adult hair follicles is sufficient to initiate the anagen phase. Scientists have discovered that the transient activation of a protein called ?-catenin can induce new hair growth.

Previous work has implicated Wnt/?-catenin signaling in embryonic hair follicle development, postnatal follicle growth and maturation, and skin tumor formation. This new work provides important insight into the role of ?-catenin as a trigger for activating the normal growth of adult hair follicles.

Researchers generated transgenic mice expressing an inactive version of ?-catenin in their skin and hair follicles. Upon topical treatment of the mice with a chemical called 4-OHT, the exogenous ?-catenin protein is activated. Thus, through the cutaneous application of 4-OHT, the researchers could transiently activate ?-catenin signaling at will.

To test the effect of ?-catenin signaling on adult hair growth, the researchers shaved the backs of telogen-phase transgenic and wild-type mice, and then applied 4-OHT once. Within 15 days, the transgenic mice grew new hair, whereas wild-type still had none . Furthermore, the new hair was histologically indistinguishable from normal hair, and progressed through the remainder of the growth cycle in stereotypical fashion.

It was found that brief activation of ?-catenin in resting hair follicles is sufficient to trigger a normal follicle growth phase, followed by the expected regression and resting phases. ?-catenin acts specifically on epithelial hair follicle progenitor cells, triggering a highly coordinated program of proliferation followed by expansion into the multiple differentiated cell types that comprise the mature, growing hair follicle. In contrast to the effects of transient and regulated beta-catenin activation, prolonged activation of ?-catenin leads to uncontrolled growth and gross distortion of the hair follicle structure, underscoring the importance of precisely controlled signaling activity for normal follicle regeneration.

 

[squeegee]

Good find Thatguy!

4-Hydroxytestosterone (4-OHT, 4,17beta-dihydroxy-4-androstene-3-one) is a legal steroidal compound that is relatively new to the market. Unlike prohormones, 4-OHT does not require enzymatic conversion to have an anabolic effect. It was first patented by G.D. Searle & Co. in 1955, but it did not reach the commercial market, and has recently become available as a dietary supplement. Chemically, 4-OHT is testosterone with a hydroxy group at the four position, making it most similar to the steroid clostebol, which has a chloro group at the four position. These two compounds are also very similar in effect.

4-OHT has moderate anabolic, mild androgenic, and anti-estrogenic properties. All in all, it can be expected to be associated with very few side effects, but this also comes at the expense of reduced anabolic activity. In the levator ani assay, 4-OHT is .65 times as anabolic and .25 times as androgenic as testosterone propionate. The reason that this compound has such low androgenic activity is that the modification at the 4 position prevents DHT conversion. In vitro, 4-OHT is actually a weak inhibitor of 5-alpha reductase. This weak androgenic effect is ideal for those who want to avoid or minimize side effects such as baldness, acne, and BPH. 4-OHT also has the benefit of having anti-estrogenic effects, which will eliminate chances of estrogen levels increasing, which can lead to side effects such as extra water retention and gyno. 4-OHT itself is a weak inhibitor of the aromatase enzyme which converts testosterone into estrogen, and a metabolite, 4-hydroxyandrostenedione (formestane), is a potent aromatase inhibitor.

Like most steroids, 4-OHT has low oral bioavailability and should be taken through a different route. Another reason why oral administration is not ideal is that, like clostebol, 4-OHT has a very short half-life. Those who inject usually use it every day or every other day totalling 300-700 mg weekly, stacked with other substances. Doses for transdermal administration should be in the range of 150-300 mg daily, and this is once again assuming one is stacking it with other steroids or prohormones. Using it as a standalone, optimal doses are probably considerably higher. 4-OHT has been most commonly stacked with 4-AD and 1-testosterone, although there are theoretical reasons why it may be beneficial to stack it with many substances – it will generally reduce estrogenic side effects, while adding anabolism without significantly contributing to androgenic side effects.

 

[squeegee]

To test the effect of ?-catenin signaling on adult hair growth, the researchers shaved the backs of telogen-phase transgenic and wild-type mice, and then applied 4-OHT once. Within 15 days, the transgenic mice grew new hair, whereas wild-type still had none . Furthermore, the new hair was histologically indistinguishable from normal hair, and progressed through the remainder of the growth cycle in stereotypical fashion.



SICK!!! I can get that stuff for cheap too!! but the hick is prolonged activation of ?-catenin leads to uncontrolled growth and gross distortion of the hair follicle structure, underscoring the importance of precisely controlled signaling activity for normal follicle regeneration.

 

[harold]

I think this is a more informal discussion of a study that found that prolonged activation of this pathway led to the formation of tumour-like growths whereas brief activation led to the growth of new follicles.
h

 

[squeegee]

This new work provides important insight into the role of ?-catenin as a trigger for activating the normal growth of adult hair follicles.If it can work for the follicles that shutdown...It will be great. It is like minoxidil on Steroids!

 

[thatdguy]

So is it wise to take orally? If so, does it interfere if you are already taking finesteride? It has an anabolic effect on it AS well as anti-dht?

So should you put it on your scalp as well?
it's easy stuff to get

thanks

 

[harold]

Slow down guys - here is the study that they are talking about. 4OHT actually refers to hydroxy-tamoxifen - and that isnt going to do anything for your hair. At least in the way you are thinking. These transgenic mice which had been modified so that part of the wnt system was under the controlf of this drug. Therefore by exposing them to 4OHT they could see what the effect of wnt was on hair. But if you havent been genetically modified in such a way you are out of luck.
hh


Oncogene. 2007 Jul 19;26(33):4882-8. Epub 2007 Feb 12.Click here to read Links
Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors.
Murayama K, Kimura T, Tarutani M, Tomooka M, Hayashi R, Okabe M, Nishida K, Itami S, Katayama I, Nakano T.

Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/beta-catenin signals. Phosphoinositide-3 kinase (PI3K)/Akt signaling regulates the 'stemness' of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.

 

[squeegee]

Hahah I know was tired last night and stupid...

 

[pproctor]

Has anyone ever heard of this?
http://www.bio-medicine.org/medicine-ne ... ility-Say-

It was found that brief activation of ?-catenin in resting hair follicles is sufficient to trigger a normal follicle growth phase, followed by the expected regression and resting phases. ?-catenin acts specifically on epithelial hair follicle progenitor cells, triggering a highly coordinated program of proliferation followed by expansion into the multiple differentiated cell types that comprise the mature, growing hair follicle. In contrast to the effects of transient and regulated beta-catenin activation, prolonged activation of ?-catenin leads to uncontrolled growth and gross distortion of the hair follicle structure, underscoring the importance of precisely controlled signaling activity for normal follicle regeneration.

Translation and some explaination: We have long known that beta-catenin can initiate the hair cycle and maybe even follicular neogenesis. Unfortunately, beta-catenin is also a cancer promoter. So this has long seemed a blind alley in hair loss treatment research. However, if possible, "transient and regulated" and "precisely controlled" beta catenin activation might have some use clinically. But ya gotta control it pretty closely or you could get "uncontrolled growth" and "gross distortion" of the hair follicle.

Peter H. Proctor, PhD,MD

 

[harold]

It doesn't seem like its a blind alley these days - pretty much all the exciting news revolves around wnt signalling. And it seems that everyon is aware that it is not something that you want to or even need to overstimulate. Timing is important as the Cotsarelis patent showed in terms of new pigmented hair formation requiring a wnt antagonist some time after its creation and the neosil BMP stuff is only applied for 21 days or something. But the real risk of cancer seems to be only if you keep "hitting" this pathway hard without letting up.
hh

Genes Dev. 2003 May 15;17(10):1219-24.Click here to read Links
Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice.
Van Mater D, Kolligs FT, Dlugosz AA, Fearon ER.

Departments of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.

Wnts have key roles in many developmental processes, including hair follicle growth and differentiation. Stabilization of beta-catenin is essential in the canonical Wnt signaling pathway. We developed transgenic mice expressing a regulated form of beta-catenin in the skin. Chronic activation of beta-catenin in resting (telogen) hair follicles resulted in changes consistent with induction of an exaggerated, aberrant growth phase (anagen). Transient activation of beta-catenin produced a normal anagen. Our data lend strong support to the notion that a Wnt/beta-catenin signal operating on hair follicle precursor cells serves as a crucial proximal signal for the telogen-anagen transition.

Development. 2004 Apr;131(8):1787-99.Click here to read Links
Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours.
Lo Celso C, Prowse DM, Watt FM.

Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

When beta-catenin signalling is disturbed from mid-gestation onwards lineage commitment is profoundly altered in postnatal mouse epidermis. We have investigated whether adult epidermis has the capacity for beta-catenin-induced lineage conversion without prior embryonic priming. We fused N-terminally truncated, stabilised beta-catenin to the ligand-binding domain of a mutant oestrogen receptor (DeltaNbeta-cateninER). DeltaNbeta-cateninER was expressed in the epidermis of transgenic mice under the control of the keratin 14 promoter and beta-catenin activity was induced in adult epidermis by topical application of 4-hydroxytamoxifen (4OHT). Within 7 days of daily 4OHT treatment resting hair follicles were recruited into the hair growth cycle and epithelial outgrowths formed from existing hair follicles and from interfollicular epidermis. The outgrowths expressed Sonic hedgehog, Patched and markers of hair follicle differentiation, indicative of de novo follicle formation. The interfollicular epidermal differentiation program was largely unaffected but after an initial wave of sebaceous gland duplication sebocyte differentiation was inhibited. A single application of 4OHT was as effective as repeated doses in inducing new follicles and growth of existing follicles. Treatment of epidermis with 4OHT for 21 days resulted in conversion of hair follicles to benign tumours resembling trichofolliculomas. The tumours were dependent on continuous activation of beta-catenin and by 28 days after removal of the drug they had largely regressed. We conclude that interfollicular epidermis and sebaceous glands retain the ability to be reprogrammed in adult life and that continuous beta-catenin signalling is required to maintain hair follicle tumours.

 

[CCS]

To test the effect of ?-catenin signaling on adult hair growth, the researchers shaved the backs of telogen-phase transgenic and wild-type mice, and then applied 4-OHT once. Within 15 days, the transgenic mice grew new hair, whereas wild-type still had none . Furthermore, the new hair was histologically indistinguishable from normal hair, and progressed through the remainder of the growth cycle in stereotypical fashion.



SICK!!! I can get that stuff for cheap too!! but the hick is prolonged activation of ?-catenin leads to uncontrolled growth and gross distortion of the hair follicle structure, underscoring the importance of precisely controlled signaling activity for normal follicle regeneration.

would that hair count as body hair? if so, wouldn't the hair growth mean hair loss on our heads?

 

[CCS]

if a body builder took that stuff, would his balls shrink?

 

[chore boy]

bump

 

[Cassin]

bump

don't waste your time

dozens and dozens of promising drugs that never make it past a few write ups.