Post Number: 152
|Posted on Friday, November 10, 2006 - 04:42 pm: ||
Im going to cut and paste from one of his responses....:
"I do not think you understand the nature of male pattern baldness. TGF-beta may be an immune regulatory molecule, but that does not mean that every person has immune response during male pattern baldness. Not every person has infiltrates of lymphocytes and leukocytes to the area of the follicle. Alopecia areata has this response, because the body begins to recognize the hair follicle itself as foreign with an all out race to destroy the hair follicle being employed by both the innate and specific sides of the immune system doing the damage.
In male pattern baldness, TGF-beta is upregulated causing the activation of fibroblasts, which deposit collagen around the follicle and cause perifollicular fibrosis. No immune response is required and an immune response is rarely seen unless the it's secondary to bacteria breaking down secretions from the sebaceous glands into proinflammatory fatty acids. This doesn't happen in every person, so there isn't an immune response.
If you think that there is an immune response, then it's your job to show that 100% of men with MPB have antibodies to the cells that make up their own hair follicles and that 100% of men with MPB have immune cell infiltrates around all follicles demonstrating miniaturization.
Cyclosporine regrows hair through mediation of a particular molecular pathway, which I will leave up to you to discover...the reason is somewhere on these forums, but I don't feel like looking for it right now. Topical steriods that cause hair regrowth do so by removing an inflammatory responses that are occurring secondary to androgenic stimulation of the sebacous glands. That's why that treatment does not work for every person.
DHT's role in the inhibition of hair growth is not a mystery. DHT binds to the androgen receptor, which is a nuclear receptor. It does so in the cytoplasm of the target cell and moves into the nucleus to act as a transcription factor. While there it seems to upregulate the expression of TGF-beta, which is the cytokine responsible for collagen deposition and fibrosis.
TGF-beta is the same molecule that causes fibrosis of the kidneys, liver, lungs, and even the heart after they are damaged and removal of this molecule during experimentation has demonstrated that the fibrosis will clear itself once the pro-fibrotic nature of TGF-beta is removed from whatever tissue it's influencing."
Baldness begins more and more to me to look like this:
DHT binds (and T to a lesser extent)
TGF beta 1, PKC, TNF-alpha, all neg-
ative growth factors get released by
the dermal papilla cells to the rest
of the follicle
follicle growth slows
immune system marker cells begin to
something about the follicle (TGF-beta
1) as foreign, and attacks it with sup-
er oxides, growth inhibitors. This
may result in constant inflammation in
Late in the game, fibrosis and shiny-
baldness is the result.
Counteracting this requires cutting DHT and T transcription to the follicle
Attempting to counteract the negative growth factors that are known (barley B-3 proanthocyanidns topically and tumeric internally would help TGF-beta 1. Apple peel proanthocyandins and grape seed proanthocyandins help Protien Kinease C activation as well as internal reservatol. Ginko Biloba and green tea catechins and a few select other things will help TNF-alpha). Ginko is even a weak alpha five reductase inhibitor. So is riboflavin if one is thinking topically.
Fighting collagen hardening and cross-linkage, which boxes in the dermal papilla cells when its time to expand. Minxoidl and Aminexil (which is just minoxidil chemcially with a little part of the molecule missing), help with this. Would have to research topical anti-fibrotics
Fighting superoxides and repairing skin damage and fighting inflammation. Copper peptides would be best at this. Coal tar, salycic acid, and ketoconazale shampoos help with inflammation and inflammatory cytokines also. Ketoconozale even inhibits androgen receptors.
One might attempt to block androgen receptors, but blocking all of the receptors all of the time is impossible with current treatments. Even RU couldn't do it constantly. Various estrogen mimickers like beta sis, tea tree oil, and lavendar oil might help some. But just going with receptor blockers would be like just going with propecia alone. Slowing the inevitable.
Ive spoken with a few about an all topical regimine that would cover much of the above with some homemade stuff for the anti-growth factors. A little apple cider vinegar, boiled beer (until you reduce volume by about a third), with some ginko biloba or green tea all mixed up as a pre-shampoo soak, left in for about 10 minutes might really help with them. Daily intake of curcumin and tocopherol might aid you more. Prox-N, Nizoral, and finasteride might do much of the rest. One would hold on to what they had for a good while with all of that.
Aderans is recruiting for phase one trials here in America. This is great news on the cloning front.
Post Number: 60
|Posted on Friday, November 10, 2006 - 05:16 pm: ||
thanks a lot for all that, jpj
Post Number: 2949
|Posted on Saturday, November 11, 2006 - 07:43 am: ||
Whole Foods sells turmeric (curcumin) at a reasonable price. It tastes good sprinkled on food and mixed in soups. An old man from India who I work out with at the gym has great hair. He told me about turmeric several years ago. I've been using it ever since. It's a miracle food - good for the prostate, hair, and who knows what else.
jpj, thanks for the gold.
Post Number: 153
|Posted on Saturday, November 11, 2006 - 11:55 am: ||
Doc had another post that has his reasoning for his regimine....which is tumeric (which I take), green tea, and vitamin E with the studies therein. He also took finasteride at the time, but doesn't now. I now know that riboflavin and ginko biloba are considered weak DHT inhibitors, so if someone is interested in the completely natural route. Here is the post:
Joined: 05 May 2006
Posted: Tue Sep 26, 2006 9:18 am Post subject: My complete treatment plan (long read)
Some people have asked me about my treatment regimen and why I use what I use. These are the best responses I can give you right now with the knowledge base I have at my disposal.
Remember, this is my plan and Iím doing it based on my findings and interpretations. Iím sort of using myself as a guinea pig. Do what you want with your body.
For DHT inhibition through inhibiting 5AR function-Proscar .75mg/day
Ė Finasteride is a potent inhibitor of 5alpha reductase type II function. This enzyme is responsible for the creation of dihydrotestosterone and dihydroprogesterone. Dihydroprogesterone is precursor to allopregnanolone, a neuroactive steroid(1). Blocking of 5AR type II decreases DHT production in the scalp.
For those who do not know, DHT works in the following manner. First it binds to the androgen receptor. The androgen/receptor complex is internalized where it moves to the nucleus of the target cell as a transcription factor. There, it initiates transcription of genes by binding to DNA regulatory elements(2). One proposed target is the TGF-beta gene , which has been shown in vitro(3).
Green Tea is on here, as well, but itís a very weak 5AR inhibitor. Its effects are multiplied when the gallate ester in EGCG is replaced with fatty acids. I do not have much information, but from what Iíve read EGCG is potent inhibitor of numerous inflammatory responses.
For PKC Downregulation
-Lots of soy products
-Vitamin E 130 IU or 333% of daily requirements in GNC multivitamin
The PKC pathway is just one of the many regulatory pathways. I donít know much about it or how it relates to TNF-alpha, but Vitamin E inhibits both the PKC and TNF-alpha pathways (4)
-Green Tea extract (630mg/day)
Green tea is known to have numerous effects on health and none of them are bad. The catechins in it are weak 5AR inhibitor and itís abilities as an antioxidant are well known. I take this because it keeps me healthy and is known to have some TNF-alpha effects.
TNF-alpha is believed to be a very important mediator of cell death and apoptosis in numerous tissues including the scalp. Numerous drugs are currently on the market that target this molecule (Enbrel, Remicade). One of the witnessed side effects of these drugs is hair regrowth. I wonít go into the mechanism of this molecule. Its effects are very similar to TGF-beta. Curcumin does affect this molecule, as well.(5)
TGF-beta down regulation
-Curcumin (300 mg twice/day)
Curcumin is a known TGF-beta inhibitor in vitro with effects being well known in studies involving kidney damage and fibrosis. Itís effects are polysystemic with it being used for arthritis, anti-cancer, gynocomastia, and Alzheimerís. Alzheimerís is said to be due TGF-beta mediated targeting of beta amyloid to neurons. Does curcumin affect this pathway (Alzheimerís) and cross the blood-brain barrier? I donít know. Curcumin is also known to increase Serotonin levels acting almost like an anti-depressant.
TGF-beta is a molecule that is known to activate the intrinsic caspase cascade within cells. The hair follicle is one such target. Numerous companies, including Scios (http://www.sciosinc.com/scios/tgf), are currently making TGF-beta inhibiting drugs for numerous diseases.
For a reason I can not discern, TGF-beta correlates with parafollicular fibrosis histologically due to increased collagen synthesis and even hair follicle malnutrition (6)(7).
References. Sorry if they are so disorganized. If more references are needed, I can get them for the drugs or studies through email if need be. Some studies are in vitro and others are in vivo, but the proposed mechanism that scientists are currently basing their research on is in a few of the articles. You can find it in article 7 in particular.
(1)A new look at the 5alpha-reductase inhibitor finasteride.
Department of Veterans Affairs Medical Research, Portland Alcohol Research Center, 97239, USA. email@example.com
Finasteride is the first 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss). These clinical applications are based on the ability of finasteride to inhibit the Type II isoform of the 5alpha-reductase enzyme, which is the predominant form in human prostate and hair follicles, and the concomitant reduction of testosterone to dihydrotestosterone (DHT). In addition to catalyzing the rate-limiting step in the reduction of testosterone, both isoforms of the 5alpha-reductase enzyme are responsible for the reduction of progesterone and deoxycorticosterone to dihydroprogesterone (DHP) and dihydrodeoxycorticosterone (DHDOC), respectively. Recent preclinical data indicate that the subsequent 3alpha-reduction of DHT, DHP and DHDOC produces steroid metabolites with rapid non-genomic effects on brain function and behavior, primarily via an enhancement of gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Consistent with their ability to enhance the action of GABA at GABA(A) receptors, these steroid derivatives (termed neuroactive steroids) possess anticonvulsant, antidepressant and anxiolytic effects in addition to altering aspects of sexual- and alcohol-related behaviors. Thus, finasteride, which inhibits both isoforms of 5alpha-reductase in rodents, has been used as a tool to manipulate neuroactive steroid levels and determine the impact on behavior. Results of some preclinical studies and clinical observations with finasteride are described in this review article. The data suggest that endogenous neuroactive steroid levels may be inversely related to symptoms of premenstrual and postpartum dysphoric disorder, catamenial epilepsy, depression, and alcohol withdrawal.
(2)Taken from Boron and Boulpaep. Medical Physiology. Updated Edition. Copyright 2005.
(3)Androgen-receptor DNA binding of TGF-beta gene in vitro and subsequent gene expression -
Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S.
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.
(4) Alpha-tocopherol decreases tumor necrosis factor-alpha mRNA and protein from activated human monocytes by inhibition of 5-lipoxygenase.
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USA. firstname.lastname@example.org
Cardiovascular disease is the leading cause of morbidity in Westernized populations. Low levels of alpha-tocopherol (AT) are associated with increased incidence of atherosclerosis and increased intakes appear to be protective. AT supplementation decreases interleukin 1 and 6 release from human monocytes. Thus, the aim of this study was to examine the effect of AT on an important proinflammatory cytokine, tumor necrosis factor-alpha (TNF) release from human monocytes. AT supplementation (1200 IU/day for 3 months) significantly decreased TNF release from activated human monocytes. Mechanisms that were examined included its effect as a general antioxidant, its inhibitory effect on protein kinase C (PKC), and the cycloxygenase-lipoxygenase pathway. While AT decreased TNF release from activated monocytes, other antioxidants had no effect on TNF release. Specific PKC inhibitors had no effect on TNF release from activated monocytes. The inhibition of TNF release by AT in activated monocytes was reversed by leukotriene B(4) (LTB(4)), a major product of the 5-lipoxygenase (5-LO) pathway. Similar observations were seen with inhibitors of 5-lipoxygenase. Indomethacin, a COX inhibitor, in the presence and absence of AT failed to affect TNF activity. These findings suggest that AT decreases TNF release from activated human monocytes via inhibition of 5-lipoxygenase. Also, AT as well as a 5-LO inhibitor significantly decreased TNF mRNA. Furthermore, AT and the 5-LO inhibitor decreased NFkappab-binding activity. Thus, in activated human monocytes, AT appears to inhibit TNF mRNA and protein by inhibition of 5-LO.
PMID: 15808419 [PubMed - indexed for MEDLINE]
(5)Curcumin: getting back to the roots.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030. email@example.com.
The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."
(6)Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al.
Transforming growth factor type beta (TGF-beta), when injected subcutaneously in newborn mice, causes formation of granulation tissue (induction of angiogenesis and activation of fibroblasts to produce collagen) at the site of injection. These effects occur within 2-3 days at dose levels than 1 microgram. Parallel in vitro studies show that TGF-beta causes marked increase of either proline or leucine incorporation into collagen in either an NRK rat fibroblast cell line or early passage human dermal fibroblasts. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) do not cause these same in vivo and in vitro effects; in both rat and human fibroblast cultures, EGF antagonizes the effects of TGF-beta on collagen formation. We have obtained further data to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of TGF-beta compared to media obtained from unactivated lymphocytes. These activated media markedly stimulate proline incorporation into collagen in NRK cells; this effect is blocked by a specific antibody to TGF-beta. The data are all compatible with the hypothesis that TGF-beta is an important mediator of tissue repair.
(7)Role of TGF-beta2 in the human hair cycle.Hibino T, Nishiyama T.
Shiseido Life Science Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan. firstname.lastname@example.org
Male pattern baldness is the result of premature entry into catagen due to androgens. In order to prevent hair loss, it is important to understand two critical steps, i.e., the induction mechanism of premature entry and the regression process of catagen. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-beta2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. TGF-beta antagonists are effective in preventing catagen-like morphological changes and in promoting elongation of hair follicles in vivo and in vitro. These lines of evidence strongly suggest the presence of a "catagen cascade" in male pattern baldness, involving: (1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network. These sequential events contribute to the shortening of the human hair cycle. Copyright 2004 Japanese Society for Investigative Dermatology
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Post Number: 49
|Posted on Saturday, November 11, 2006 - 01:09 pm: ||
JPJ. I have a question that you propably have an answer to. Is it possible that dht blockers like fina or dut, can transorm DNA, so that the body does not produce the same amounts of DHT, as it did before treatment... is it possible that any drug can harm body chemistry long after you finished treatment... I realy wonder because I 4 ears on fina and 3 months on dut I have less dht and less hairloss and energy in consequence.
Doctor told me that I am a lunatic...
Post Number: 154
|Posted on Saturday, November 11, 2006 - 06:41 pm: ||
The alpha five reductase type two enzymes that converts T to DHT are located in the outer root sheaths of head hair follicles, the beard area, and the prostate.
The type one alpha five enzymes are located in the kidney, liver, adrenal gland, chest and back skin, sebaceous glands all over the body, and sweat glands.
Finas chemically binds with the enzyme, making it unable to change T into DHT. It takes about two weeks for DHT levels to rebound fully in the body after halting finasteride usage. Dutasteride on the other hand, lasts much longer and can be active in the bod for about a year after halting its usage.
When you get on finas or dutas, there will be more testosterone around because alot of the T that would have gotten changed into DHT wont be changed. Youre hair androgen receptors up their activity and numbers somehow also.
DHT is the most active form of testosterone. On dutas especially, you might notice a difference in how you feel. Type one DHT is near alot of your internal organs............and they will be recieving less androgenic stimulation by you only producing half your normal levels of Type one DHT. However, type two is in hair follicles and the prostate..........so cutting it shouldn't affect how you feel very much because DHT tends not to travel all that well in the body anyway. The dutas might make you a bit sluggish and have a bit less of a sex drive. This is something Ive seen in forums over and over. Even the great Almighty God of Hairloss stated he cant wait for cloning so he could get off dutasteride and "feel like a man again". I remembered that he said that because he is extremely intelligent.
Dutas is pretty damn strong stuff.
Post Number: 50
|Posted on Sunday, November 12, 2006 - 08:03 am: ||
Ok. But is it possible that some effects of long term usage of these drugs may last forever...
like dizzines.. lover libido, body fat retention.. lower energy.. etc.. is it possible or I am rather a lunatic..
Post Number: 156
|Posted on Sunday, November 12, 2006 - 06:23 pm: ||
I would imagine after a year or so off dutasteride you should pretty much be back to normal. Thats just my opinion however. Perhaps you could do a web search of men whove used avodart for BPH for several years.