docj077
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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 I’m doing it based on my findings and interpretations. I’m sort of using myself as a guinea pig. Do what you want with your body.
Enjoy
For DHT inhibition through inhibiting 5AR function-Proscar .75mg/day
– 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 it’s 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 I’ve 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 don’t know much about it or how it relates to TNF-alpha, but Vitamin E inhibits both the PKC and TNF-alpha pathways (4)
TNF-alpha downregulation
-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 it’s abilities as an antioxidant are well known. I take this because it keeps me healthy and is known to have some TNF-alpha effects.
-Curcumin(see below)
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 won’t 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. It’s effects are polysystemic with it being used for arthritis, anti-cancer, gynocomastia, and Alzheimer’s. Alzheimer’s is said to be due TGF-beta mediated targeting of beta amyloid to neurons. Does curcumin affect this pathway (Alzheimer’s) and cross the blood-brain barrier? I don’t 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. finnd@ohsu.edu
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 (Androgenetic Alopecia) 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 Androgenetic Alopecia. 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 Androgenetic Alopecia 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.
Devaraj S,
Jialal I.
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USA. sridevi.devaraj@ucdmc.ucdavis.edu
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. aggarwal@mdanderson.org.
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. toshihiko.hibino@to.shiseido.co.jp
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
Remember, this is my plan and I’m doing it based on my findings and interpretations. I’m sort of using myself as a guinea pig. Do what you want with your body.
Enjoy
For DHT inhibition through inhibiting 5AR function-Proscar .75mg/day
– 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 it’s 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 I’ve 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 don’t know much about it or how it relates to TNF-alpha, but Vitamin E inhibits both the PKC and TNF-alpha pathways (4)
TNF-alpha downregulation
-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 it’s abilities as an antioxidant are well known. I take this because it keeps me healthy and is known to have some TNF-alpha effects.
-Curcumin(see below)
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 won’t 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. It’s effects are polysystemic with it being used for arthritis, anti-cancer, gynocomastia, and Alzheimer’s. Alzheimer’s is said to be due TGF-beta mediated targeting of beta amyloid to neurons. Does curcumin affect this pathway (Alzheimer’s) and cross the blood-brain barrier? I don’t 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. finnd@ohsu.edu
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 (Androgenetic Alopecia) 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 Androgenetic Alopecia. 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 Androgenetic Alopecia 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.
Devaraj S,
Jialal I.
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USA. sridevi.devaraj@ucdmc.ucdavis.edu
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. aggarwal@mdanderson.org.
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. toshihiko.hibino@to.shiseido.co.jp
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
