Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells.
Arch Dermatol Res. 2008 Mar;300(3):147-52.
Dihydrotestosterone inhibits murine hair growth via the androgen receptor.
Br J Dermatol. 2008 Jun 11.
Purinergic receptors are part of a signalling system for proliferation and
differentiation in distinct cell lineages in human anagen hair follicles.
Purinergic Signal. 2008 May 27.
Hair growth promoting activity of Eclipta alba in male albino rats.
Arch Dermatol Res. 2008 May 14
Control of thrombin signaling through PI3K is a mechanism underlying plasticity
between hair follicle dermal sheath and papilla cells.
J Cell Sci. 2008 Apr 8
Protective effects of taurine on human hair follicle grown in vitro
Int J Cosmet Sci. 2006 Aug;28(4):289-98
Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles.
J Endocrinol. 2008 Apr;197(1):11-23.
The role of Smads in skin development.
J Invest Dermatol. 2008 Apr;128(4):783-90.
trans-3,4'-Dimethyl-3-hydroxyflavanone, a hair growth enhancing active
component, decreases active transforming growth factor beta2 (TGF-beta2) through
control of urokinase-type plasminogen activator (uPA) on the surface of
keratinocytes.
Biol Pharm Bull. 2008 Mar;31(3):449-53.
Baldness and myocardial infarction in men: the atherosclerosis risk in communities study.
Am J Epidemiol. 2008 Mar 15;167(6):676-83.
Female pattern hair loss may be triggered by low oestrogen to androgen ratio.
Endocr Regul. 2008 Mar;42(1):13-6.
Expression of NAD(+) dependent 15-hydroxyprostaglandin dehydrogenase and protection of prostaglandins in human hair follicle.
Exp Dermatol. 2008 Mar 4
Effect of topical application of raspberry ketone on dermal production of
insulin-like growth factor-I
in mice and on hair growth and skin elasticity in
humans.
Growth Horm IGF Res. 2008 Mar 3
Differing responses of human follicular and nonfollicular scalp cells in an in
vitro wound healing assay:
Effects of estrogen on vascular endothelial growth
factor secretion.
Wound Repair Regen. 2008 Mar;16(2):243-253.
Epithelial fibroblast growth factor receptor 1 regulates enamel formation.
J Dent Res. 2008 Mar;87(3):238-43.
G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance
of human hair growth.
Nat Genet. 2008 Feb 24
Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes.
J Invest Dermatol. 2008 Feb;128(2):262-9.
BMP signaling in dermal papilla cells is required for their hair
follicle-inductive properties.
Genes Dev. 2008 Feb 15;22(4):543-57.
Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil.
FASEB J. 2008 Feb 7
Sustained epithelial {beta}-catenin activity induces precocious
hair development but disrupts hair follicle down-growth and hair shaft
formation.
Development. 2008 Feb 6
Different patterns of 5alpha-reductase expression, cellular
distribution, and testosterone metabolism in human follicular dermal
papilla cells.
Biochem Biophys Res Commun. 2008 Feb 4
Functional role of beta1 integrin-mediated signaling in the human hair
follicle.
Exp Cell Res. 2008 Feb 1;314(3):498-508.
Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft
growth.
Biochem Biophys Res Commun. 2008 Mar 7;367(2):299-304.
Melatonin and the hair follicle.
J Pineal Res. 2008 Jan;44(1):1-15.
Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum
leaf.
Biol Pharm Bull. 2007 Dec;30(12):2402-5.
Proteasome inhibitors stimulate both bone formation and hair growth by similar
mechanisms.
Ann N Y Acad Sci. 2007 Nov;1117:298-301.
Probing the effects of stress mediators on the human hair follicle: substance P
holds central position.
Am J Pathol. 2007 Dec;171(6):1872-86.
Prostanoid receptors in anagen human hair follicles.
Exp Dermatol. 2008 Jan;17(1):63-72.
Premature Senescence of Balding Dermal Papilla Cells In Vitro Is Associated with
p16(INK4a) Expression.
J Invest Dermatol. 2007 Nov 8
Interleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed
factor with hair growth inhibitory properties.
Exp Dermatol. 2008 Jan;17(1):12-9.
Repigmentation of gray hair after thyroid hormone treatment
Actas Dermosifiliogr. 2007 Nov;98(9):603-10.
Telomerase reverses epidermal hair follicle stem cell defects and loss of
long-term survival associated with critically short telomeres.
J Cell Biol. 2007 Oct 22;179(2):277-90.
Thymosin beta 4 induces hair growth via stem cell migration and differentiation.
Ann N Y Acad Sci. 2007 Sep;1112:95-103
L-carnitine-L-tartrate promotes human hair growth in vitro.
Exp Dermatol. 2007 Nov;16(11):936-45.
Prostaglandin metabolism in human hair follicle.
Exp Dermatol. 2007 Sep;16(9):762-9.
Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells
causes apoptosis in follicular keratinocytes.
J Invest Dermatol. 2008 Feb;128(2):262-9.
Transforming growth factor-beta receptor II is preferentially expressed in the
companion layer of the human anagen hair follicle.
Br J Dermatol. 2007 Jul;157(1):161-4.
Administration of capsaicin and isoflavone promotes hair growth by increasing
insulin-like growth factor-I production in mice and in humans with alopecia.
Growth Horm IGF Res. 2007 Oct;17(5):408-15.
Phospholipase A(2) and Phospholipase B activities in fungi.
Biochim Biophys Acta. 2006 Nov;1761(11):1391-9
Bone
morphogenetic protein signaling regulates the size of hair follicles
and modulates the expression of cell cycle-associated genes.
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18166-71.
Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH.
Science. 2006 Nov 10;314(5801):982-5.
Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).
Phytomedicine. 2006 Nov 6
Keratinocyte
growth factor protects epidermis and hair follicles from cell death
induced by UV irradiation, chemotherapeutic or cytotoxic agents.
J Cell Sci. 2006 Dec 1;119(Pt 23):4841-9. Epub 2006 Nov 7
Prolactin delays hair regrowth in mice.
J Endocrinol. 2006 Nov;191(2):415-25.
The hair follicle as an estrogen target and source.
Endocr Rev. 2006 Oct;27(6):677-706.
Influence of interleukin-1alpha on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells.
Exp Dermatol. 2006 Oct;15(10):784-93.
Finasteride induced depression: a prospective study.
October 2006 BMC Clinical Pharmacology 2006, 6:7
Nourkrin: objective and subjective effects and tolerability in persons with hair loss.
J Int Med Res. 2006 Sep-Oct;34(5):514-9.
Smad7-induced beta-catenin degradation alters epidermal appendage development.
Dev Cell. 2006 Sep;11(3):301-12.
Citrus
polymethoxylated flavones improve lipid and glucose homeostasis and
modulate adipocytokines in fructose-induced insulin resistant hamsters.
Life Sci. 2006 Jun 20;79(4):365-73.
The influence of maca (Lepidium meyenii) on antioxidant status, lipid and glucose metabolism in rat.
Plant Foods Hum Nutr. 2007 Jun;62(2):59-63.
[2005]
Dose-response
effects of phytoestrogens on the activity and expression of
3beta-hydroxysteroid dehydrogenase and aromatase in human
granulosa-luteal cells.
J Steroid Biochem Mol Biol. 2005 Aug;96(3-4):279-86.
Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles.
Br J Dermatol. 2005 Apr;152(4):623-31.
[2004]
Caffeine induces sonic hedgehog gene expression in cultured astrocytes and neurons.
J Mol Neurosci. 2004;24(2):201-5.
Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats.
Diabetes Obes Metab. 2004 May;6(3):200-7.
Causes of hair loss and the developments in hair rejuvenation (Women need L-Lysine).
Int J Cosmet Sci. 2002 Feb;24(1):17-23.
Below (not in chronological order)
Cancer Res. 2006 Jan 15;66(2):613-621.
Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
J Altern Complement Med. 2003 Feb;9(1):161-8.
Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.
Mechanisms of Ageing and Development, Volume 114, Issue 3, 14 April 2000, Pages 207-21
Tumori. 1987 Feb 28;73(1):29-31.
J Environ Pathol Toxicol Oncol. 2003;22(1):49-58.
Role of TGF-beta2 in the human hair cycle.
J. Dermatol Sci. 2004 Jun;35(1):9-18.
A potential suppressor of TGF-beta delays catagen progression in hair follicles.
J. Investig Dermatol Symp Proc. 2003 Jun;8(1):65-8.
Ellagic Acid, An Anti-oxidative suppressor of TFG-b prolongs anagen phase of murine hair follicles
AmorePacific R&D Center, Yongin-si, Korea
Stem cells in the skin: waste not, Wnt not
Vol. 17, No. 10, pp. 1189-1200, May 15, 2003
Role of androgen in mesenchymal epithelial interactions in human hair follicle.
J Investig Dermatol Symp Proc. 2005 Dec;10(3):209-11.
There are many more steroidogenic enzymes involved in the onset and development of AGA
The
synthesis of testosterone in the gonads involve the four enzymes
cytochrome P-450 side-chain cleavage enzyme, cytochrome P-450
17a-hydroxylase/lyase, 3b-hydroxysteroid dehydrogenase, and
17b-hydroxysteroid dehydrogenase.
Dermatology. 2003;206(2):85-95.
Flavonoid inhibition of overexpressed human 3beta-hydroxysteroid dehydrogenase type II.
J Steroid Biochem Mol Biol. 2004 Feb;88(2):175-82.
delta 5-3 beta-hydroxysteroid dehydrogenase activity in sebaceous glands of scalp in male-pattern baldness.
J. Invest Dermatol 1988 Aug;91(2):101-5.
Steroidogenic enzymes in skin.
Eur. J Dermatol 2001 Jul-Aug;11(4):293-5.
Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal axis and synthesize cortisol.
FASEB J. 2005 Aug;19(10):1332-4. Epub 2005 Jun 9.
Hormonal profile of men with premature balding.
Exp Clin Endocrinol Diabetes 2004 Jan;112(1):24-8.
Hormonal profile in men with premature androgenic alopecia
Cb Lek. 2000;101(1):17-22.
Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
PNAS | May 14, 2002 | vol. 99 | no. 10 | 7148-7153
Hormonal interaction and hair growth
Ann Dermatol Venereol 2002 May;129(5 Pt 2):787-92.
Treatment
of benign prostatic hyperplasia. Results of a treatment study with the
phytogenic combination of Sabal extract WS 1473 and Urtica extract WS
1031 in urologic specialty practices
Fortschr med. 1995 Jan 30;113(3):37-40.
Patients with a large prostate show a higher prevalence of androgenetic alopecia.
Journal of urology 005 Nov;174(5):1905.
Perception of Men with Androgenetic Alopecia by Women and Nonbalding Men
Irreversibility of hair follicle changes after 30 months of Androgenetic Alopecia.
The Hair-Growing Activity of Procyanidin Oligomers
Androgens in Human Hair Follicles
S. Itami. Osaka University School of Medicine, Osaka, Japan.
Hormonal interaction and hair growth
Ann Dermatol Venereo 2002 May;129(5 Pt 2):787-92.l
Protection from chemotherapy-induced alopecia by docosahexaenoic acid.
Lipids 1999;34 Suppl:S105.
Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.
Biochem J. 1992 July 15; 285(Pt 2): 557–562.
Androgen action: molecular mechanism and medical application.
J Formos Med Assocation 1994 Sep;93(9):741-51.
Growth
suppression of hamster flank organs by topical application of
gamma-linolenic and other fatty acid inhibitors of 5alpha-reductase.
J Invest Dermatol 1997 Aug;109(2):152-7.
Antioxidants and lipid peroxidation status in the blood of patients with alopecia.
Cell Biochem Funct. 2000 Sep;18(3):169-73.
Glutathione, glutathione S-transferase and reactive oxygen species of human scalp sebaceous glands in male pattern baldness.
J Invest Dermatol 1996 Aug;107(2):154-8.
Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate.
Biochem Biophys Res Commun. 1995 Sep 25;214(3):833-8.
Orally
Administered Green Tea Polyphenols Prevent Ultraviolet
Radiation-Induced Skin Cancer in Mice through Activation of Cytotoxic T
Cells and Inhibition of Angiogenesis in Tumors.
J Nutr 2005 Dec;135(12):2871-7
Tea
polyphenol epigallocatechin 3-gallate impedes the anti-apoptotic
effects of low-grade repetitive stress through inhibition of Akt and
NFkappaB survival pathways.
FEBS Letter 2006 Jan 9;580(1):278-84.
Mechanisms of cancer prevention by tea polyphenols based on inhibition of TNF-alpha expression.
Biofactors 2000;13(1-4):67-72.
Opposing action of curcumin and green tea polyphenol in human keratinocytes.
Mol Nutr Food Res 2006 Jan 10
The effects of tea polyphenolic compounds on hair loss among rodents.
J Natl Med Assoc. 2005 Aug;97(8):1165-9.
Effect of Coapplication of Capsaicin and Minoxidil on the Murine Hair Growth
Won-Soo Lee, Hyung Jin Ahn, Young Hee Kim Department of Dermatology. Yonsei University Wonju College of Medicine, Wonju. Korea
Stress
inhibits hair growth in mice by induction of premature catagen
development and deleterious perifollicular inflammatory events via
neuropeptide substance P-dependent pathways.
Am J Pathol 2003 Mar;162(3):803-14.
Synergistic Capsicum-tea mixtures with anticancer activity.
J Pharm Pharmacol 2003 Jul;55(7):987-94.
Anticancer activity of grape and grape skin extracts alone and combined with green tea infusions.
Cancer Lett. 2005 Aug 26
The effect of taurine and its derivatives on the hair follicle cell
Journal of Investigative Dermatology, Volume 121 Issue 2 Page 354 - August 2003
doi:10.1046/j.1523-1747.2003.12366.x
Taurine prevents fructose-diet induced collagen abnormalities
J Diabetes Complications 2005 Sep-Oct;19(5):305-11.
A Hot New Twist to Hair Biology
Androgen-inducible
TGF-ß1 from balding dermal papilla cells inhibits epithelial cell
growth: a clue to understand paradoxical effects of androgen on human
hair growth
The FASEB Journal. 2002;16:1967-1969.
Glutathione, glutathione S-transferase and reactive oxygen species of human scalp sebaceous glands in male pattern baldness.
J. Invest Dermatol 1996 Aug;107(2):154-8.
Nitric
oxide in the human hair follicle: constitutive and
dihydrotestosterone-induced nitric oxide synthase expression and NO
production in dermal papilla cells.
J Mol Med. 2003 Feb;81(2):110-7. Epub 2002 Dec 19.
A Significant Role of Aromatase Cytochrome P450 on Hair Re-growth and Pigmentation.
A.
Ohuchi1, K. Ohguchi1, N. Tsuji1, S. Moriwaki1, Y. Takema1, S. Honda2,
N. Harada2 Biological Science Laboratories, Kao Corp. Tochigi, Japan1
and Dept. of Bio-chemistry, Fujita Health University School of
Medicine, Aichi, Japan2
The Clinical Importance of the Metabolite Equol—A Clue to the Effectiveness of Soy and Its Isoflavones
J. Nutr. 132:3577-3584, December 2002
Equol Is a Novel Anti-Androgen that Inhibits Prostate Growth and Hormone Feedback
BIOLOGY OF REPRODUCTION 70, 1188–1195 (2004)
DOI: 10.1095/biolreprod.103.023713
Equol Is a Novel Anti-Androgen that Inhibits Prostate Growth and Hormone Feedback
Biol Reprod. 2004 Apr;70(4):1188-95. Epub 2003 Dec 17.
S-Equol, a
potent ligand for estrogen receptor ß, is the exclusive enantiomeric
form of the soy isoflavone metabolite produced by human intestinal
bacterial flora
American Journal of Clinical Nutrition, Vol. 81, No. 5, 1072-1079, May 2005
Humans
have acquired an ability to exclusively synthesize S-equol from
daidzein, and it is significant that, unlike R-equol, the S enantiomer
has a relatively high affinity for estrogen receptor beta. A newly
isolated rod-shaped, gram-negative anaerobic bacterium from human
feces, named Julong 732, was found to be capable of metabolizing the
isoflavone dihydrodaidzein to S-equol under anaerobic conditions.
Higher consumption of green tea may enhance equol production.
Asian Pac J Cancer Prev. 2003 Aug-Dec;4(4):297-301.
Long-Term Dietary Habits Affect Soy Isoflavone Metabolism and Accumulation in Prostatic Fluid in Caucasian Men: Meat consumption coupled with Daidzein (isoflavone) intake increases probability of Equol production.
J. Nutr. 135:1400-1406, June 2005
The Molecular Basis of Tooth Development and Its Implications in Signaling Systems in Hair Development
Ichiro
Satokata Div. of Developmental Biology, Dept. of Oral Biological
Science, Niigata University Graduate School of Medical and Dental
Sciences, Niigata, Japan
Study
points to insulin resistance in AGA hair loss. As if the stress (ACTH)
were not enough, here's more proof that impaired blood sugar metabolism
can exacerbate hair loss.
Med Hypotheses. 2002 Apr;58(4):261-3.
Neuroimmunoendocrine circuitry of the 'brain-skin connection'.
Trends Immunol 2006 Jan;27(1):32-9.
Regulation of PDGF and PDGF receptor in cultured dermal papilla cells and follicular keratinocytes of the human hair follicle.
Exp Dermatol. 2003 Oct;12(5):662-72.
Early androgenetic alopecia as a marker of insulin resistance.
Lancet. 2000 Sep 30;356(9236):1165-6.
The
expression of insulin-like growth factor 1 in follicular dermal
papillae correlates with therapeutic efficacy of finasteride in
androgenetic alopecia.
J Am Adac Dermatol 2003 Aug;49(2):229-33.
Circulating insulin-like growth factors in patients infected with Helicobacter pylori.
Clin. Biochem 2004 Nov;37(11):997-1001.
High glycemic index carbohydrate mediates an acute proinflammatory process as measured by NF-kappaB activation.
Asia Pac J Clin Nutr. 2005;14 Suppl:S120.
Nutrition-endocrine
interactions: induction of reciprocal changes in the delta 4-5
alpha-reduction of testosterone and the cytochrome P-450-dependent
oxidation of estradiol by dietary macronutrients in man.
Proc Natl Acad Sci U S A. 1983 December; 80(24): 7646–7649.
(IGF-1)
and androgens, while simultaneously reducing insulin-like growth
factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin
(SHBG).
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 2003 Sep;136(1):95-112.
Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia.
Br J Dermatol 1983 Sep;109(3):249-52.
What may be the markers of the male equivalent of polycystic ovary syndrome?
Physiol Res. 2004;53(3):287-94.
An
adjunctive preventive treatment for heart disease and a set of
diagnostic tests to detect it: Insulin-like growth factor-1 deficiency
and cell membrane pathology are an inevitable cause of heart disease.
Med Hypotheses 2006 Jan 9
Acne vulgaris: a disease of Western civilization.
Arch Dermatol 2002 Dec;138(12):1584-90.
Early Onset Baldness and Prostate Cancer Risk
http://cebp.aacrjournals.org/cgi/content/full/9/3/325
Vertex Balding Associated with Prostate Cancer: Findings from an Australian Case-Control Study
Cancer Epidemiology Biomarkers & Prevention Vol. 11, 549-553, June 2002
Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids
Journal of Endocrinology, Vol 147, Issue 2, 295-302
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Effect
of dietary components, including lignans and phytoestrogens, on
enterohepatic circulation and liver metabolism of estrogens and on sex
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Mammalian lignan production from various foods.
Nutr Cancer. 1991;16(1):43-52.
Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed.
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Urinary steroid measurements in some endocrine and psychiatric diseases.
Curr Med Chem. 2005;12(11):1339-42.
Use of emu oil for stimulating skin and hair growth
United States Patent: 5,958,384 Holick, September 28, 1999
Analysis of apoptotic cell death in human hair follicles in vivo and in vitro.
J. Invest Dermatol 1998 Dec;111(6):948-54.
Polysaccharide
purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated
apoptosis in human neutrophils through activation of the
phosphatidylinositol 3 kinase/Akt signaling pathway.
J Leukoc Biol. 2002 Jul;72(1):207-16.
Isolation of soluble yeast beta-glucans that inhibit human monocyte phagocytosis mediated by beta-glucan receptors
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Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines.
Food Chem Toxicol 2001 Nov;39(11):1087-94.
Estrogens and the hair follicle.
J Dtsch Dermatol Ges. 2004 Jun;2(6):412-23.
Equol-Producing Bacteria and Estrogen Metabolism
A
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effectiveness of botanically derived inhibitors of 5-alpha-reductase in
the treatment of androgenetic alopecia.
J Altern Complement Med. 2002 Apr;8(2):143-52.
Identification
of clustered cells in human hair follicle responsible for MMP-9
gelatinolytic activity: consequences for the regulation of hair growth.
Int J Dermatol. 2001 Jun;40(6):385-92.
Human
Scalp Dermal Papilla and Fibrous Sheath Cells have a different
expression profile of Matrix Metalloproteinases in vitro when compared
to Scalp Dermal Fibroblasts.
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Anti-inflammatory and antipyretic activities of beta-sitosterol.
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Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate.
Proc West Pharmacol Soc. 2003;46:153-5.
ß-Sitosterol,
ß-Sitosterol Glucoside, and a Mixture of ß-Sitosterol and ß-Sitosterol
Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer
Cells In Vitro and in Ovariectomized Athymic Mice
American Society for Nutritional Sciences J. Nutr. 134:1145-1151, May 2004
The Importance of Sitosterol and Sitosterolin
in human and animal nutrition
Department of Chemistry and Applied Chemistry of Natal, Durban, 4041 South Africa
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Plant-Based Fat Inhibits Cancer-Cell Growth By Enhancing Cell's Signaling System, UB Researchers Show
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Early Onset Baldness and Prostate Cancer Risk
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Flaxseed supplementation significantly increased urinary 2-hydroxyestrone secretion
American Journal of Clinical Nutrition, Vol. 79, No. 2, 318-325, February 2004
Intestinal Bacterial Communities That Produce Active Estrogen-Like Compounds Enterodiol and Enterolactone in Humans
Applied and Environmental Microbiology, October 2005, p. 6077-6085, Vol. 71, No. 10
Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside.
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Polymorphisms
in the CYP19 gene may affect the positive correlations between serum
and urine phytoestrogen metabolites and plasma androgen concentrations
in men.
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Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG).
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Secoisolariciresinol diglucoside from flaxseed delays the development of type 2 diabetes in Zucker rat.
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The Effect of Flax Seed Cultivars with Differing Content of Alpha Linolenic Acid and Lignans on Responses to Mental Stress
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Pharmacokinetics of Enterolignans in Healthy Men and Women Consuming a Single Dose of Secoisolariciresinol Diglucoside
American Society for Nutritional Sciences J. Nutr. 135:795-801, April 2005
The Relative Bioavailability of Enterolignans in Humans Is Enhanced by Milling and Crushing of Flaxseed
American Society for Nutritional Sciences J. Nutr. 135:2812-2816, December 2005
Studies on the metabolism of the plant lignans secoisolariciresinol and matairesinol.
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Antioxidant
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its mammalian lignan metabolites enterodiol and enterolactone.
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Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells.
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Androgenetic alopecia in women and Coronary Heart Disease in Women
http://dermatology.cdlib.org/113/original/androgenetic/mortazavi.html
Androgenetic alopecia in women.
J Investig Dermatol Symp Proc. 2003 Jun;8(1):24-7.
Different
levels of 5alpha-reductase type I and II, aromatase, and androgen
receptor in hair follicles of women and men with androgenetic alopecia.
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Current understanding of androgenetic alopecia. Part I: etiopathogenesis
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Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin.
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CD200, a "no danger" signal for hair follicles.
J Dermatol Sci. 2005 Dec 28
Photochemopreventive
Effect of Pomegranate Fruit Extract on UVA-mediated Activation of
Cellular Pathways in Normal Human Epidermal Keratinocytes.
Photochem Photobiol June 2005
Pomegranate
as a cosmeceutical source: Pomegranate fractions promote proliferation
and procollagen synthesis and inhibit matrix metalloproteinase-1
production in human skin cells.
J Ethnopharmacol 2005 Oct 8
Pomegranate
juice reduces oxidized low-density lipoprotein downregulation of
endothelial nitric oxide synthase in human coronary endothelial cells
Nitric Oxide 2006 Jan 11
Pomegranate
flower extract diminishes cardiac fibrosis in Zucker diabetic fatty
rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB
pathways.
J Cardiovasc Pharmacol 2005 Dec;46(6):856-62.
Development and progression of alopecia in the vitamin D receptor null mouse.
J. Cell Physiol 2006 Jan 17
Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions.
Calcif Tissue Int. 2005 Nov;77(5):311-8.
Investigation
of the topical application of procyanidin oligomers. from apples to
identify their potential use as a hair-growing agent.
http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1473-2165.2005.00199.x
BMP signaling in the control of skin development and hair follicle growth.
Differentiation 2004 Dec;72(9-10):512-26.
5alpha-reductase 2 inhibition impairs brain defeminization of male rats: reproductive aspects.
Pharmacol Biochem Behave 2005 Sep;82(1):228-35.
Terminalia
arjuna (Roxb.) protects rabbit heart against ischemic-reperfusion
injury: role of antioxidant enzymes and heat shock protein.
J Enthopharmacol 2005 Jan 15;96(3):403-9. Epub 2004 Nov 21.
Aminophospholipid
glycation and its inhibitor screening system: A new role of pyridoxal
5'-phosphate and pyridoxal as lipid glycation inhibitor.
J. Lipid Res.2006 Feb 9
The hair growth promoting effect of ascorbic acid 2-phosphate, a long-acting Vitamin C derivative.
J. Dermatol Sci. 2006 Feb;41(2):150-2. Epub 2006 Jan 9.
Human Scalp
Hair Follicles Are Both a Target and a Source of Prolactin, which
Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven
Hair Follicle Regression
American Journal of Pathology. 2006;168:748-756.
The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects.
Exp Clin Endocrinol Diabetes 1996;104(6):447-53.
Benfotiamine prevents the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3
Diabetologia 2006 Feb;49(2):405-20. Epub 2006 Jan 17.
Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome.
J. Clin Endocrinol Metab. 2006 Mar;91(3):1173-7. Epub 2005 Dec 6.
Premature androgenic alopecia and insulin resistance. Male equivalent of polycystic ovary syndrome?
Endocr Regul. 2005 Dec;39(4):127-31.
Inhibitory
autocrine factors produced by the mesenchyme-derived hair follicle
dermal papilla may be a key to male pattern baldness.
Br J. Dermatol 2006 Apr;154(4):609-18.
Biological characterization of cultured dermal papilla cells and hair follicle regeneration in vitro and in vivo.
Chinese Medical Journal, 2006, Vol. 119 No. 4 : 275-281
Induction of versican by ascorbic acid 2-phosphate in dermal papilla cells.
J Dermatol Sci. 2006 Apr 4
Focus on prolactin as a metabolic hormone.
Trends Endocrinol Metab. 2006 Apr;17(3):110-6
Epithelial-mesenchymal interaction and hair cycling
Shiseido Life Science Research Center, MGH/Harvard Cutaneous Biology Research Center
PDGF isoforms induce and maintain anagen phase of murine hair follicles.
J Dermatol Sci. 2006 May 22
Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):169-76.
Exploring link between Estrogen and hair growth
Dermatology Times 2003
Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds
Cancer Research 63, 8516-8522, December 1, 2003
Pathomechanism of androgenetic alopecia and new treatment
Nippon Ronen Igakkai Zasshi. 2004 Nov;41(6):598-600.
Interleukin-1beta
is differentially expressed by human dermal papilla cells in response
to PKC activation and is a potent inhibitor of human hair follicle
growth in organ culture.
J Interferon Cytokine Res. 1997 Mar;17(3):151-7.
Hormone studies in females with androgenic hairloss.
Gynecol Obstet Invest. 1991;31(4):235-9.
P35
HAIR CARE FORMULATIONS CONTAINING CARNITINE DERIVATIVES ACTIVATE
CELLULAR ENERGY METABOLISM AND BOOST THE ATP CONTENT IN HUMAN HAIR
FOLLICLES
Hair Loss Research Society 2005
Researchers Indentify Signals that Cause Hair Follicles to Sprout
Howard Hughes Medical Institute March 20th, 2003
In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus.
Maturitas. 2006 Aug 21
A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control.
Am J Pathol. 2005 Apr;166(4):985-98.
Stress
Inhibits Hair Growth in Mice by Induction of Premature Catagen
Development and Deleterious Perifollicular Inflammatory Events via
Neuropeptide Substance P-Dependent Pathways.
American Journal of Pathology. 2003;162:803-814
p53 Involvement in the Control of Murine Hair Follicle Regression
American Journal of Pathology. 2001;158:1913-1919.
Stress and the Hair Follicle
American Journal of Pathology. 2003;162:709-712.
Prolactin
and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show
Hair Cycle-Dependent Expression, and Induce Catagen
American Journal of Pathology. 2003;162:1611-1621.
Cyclosporin
A-induced hair growth in mice is associated with inhibition of
calcineurin-dependent activation of NFAT in follicular keratinocytes
Am J Physiol Cell Physiol 284: C1593-C1603, 2003; doi:10.1152/ajpcell.00537.2002
Neurogenic Inflammation in Stress-Induced Termination of Murine Hair Growth Is Promoted by Nerve Growth Factor
Hair growth inhibition by psychoemotional stress: a mouse model for neural mechanisms in hair growth control.
Exp Dermatol. 2006 Jan;15(1):1-13.
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The most important study on hair loss listed to date:
| Androgenetic
alopecia and microinflammation |
Yann
F. Mahé,PhD, Jean-François
Michelet,MSc, Nelly Billoni, MSc, Françoise
Jarrousse, BTS , Bruno Buan, BTS , Stephane
Commo, BTS, Didier Saint-Léger,PhD
and Bruno A. Bernard,PhD
International Journal of Dermatology
Volume 39 Issue 8 Page 576
- August 2000
|
|
Today,
androgenetic alopecia (AGA) is considered
to be an alteration of hair growth and/or
a premature aging of the pilosebaceous unit
with a multifactorial and even polygenic
etiology. 1
The fact that the success rate of treatment
with either antihypertensive agents, or
modulators of androgen metabolism, barely
exceeds 30% means that other pathways may
be envisioned. The implication of various
activators of inflammation in the etiology
of AGA has progressively and recently emerged
from several independent studies. 2,3,4,5,6,7,8,9,10,11
A fibroplasia of the dermal sheath,
which surrounds the hair follicle, is now
suspected to be a common terminal process
resulting in the miniaturization and involution
of the pilosebaceous unit in AGA. 2
8 We review here several observations
underlining the possible implication of
a slow, silent, and painless process in
AGA. Because we think that it should not
be confused with a classical inflammatory
process, we have called it microinflammation.
An early study referred to an inflammatory
infiltrate of mononuclear cells and lymphocytes
in about 50% of the scalp samples studied.
2
Another more recent study by Jaworsky
et al . 3
confirmed an inflammatory infiltrate
of activated T cells and macrophages in
the upper third of the hair follicles from
transitional regions of alopecia (i.e. which
are characterized by actively progressing
alopecia). This study also reported the
occurrence of a developing fibrosis of the
perifollicular sheath, together with the
degranulation of follicular adventitial
mast cells. The miniaturization
of the hair follicles was found to be associated
with a deposit of so-called "collagen or
connective tissue streamers" beneath the
follicle, 2,7
as well as a 2 2.5 times enlargement
of the follicular dermal sheath composed
of densely packed collagen bundles.
3
This thickening of the dermal sheath
in progression zones of AGA has also recently
been observed in our laboratory using immunohistochemical
staining ( Fig. 1
).
Horizontal
section studies of scalp biopsies indicate
that the so-called perifollicular fibrosis
is generally mild, consisting of loose,
concentric layers of fibrotic collagen that
must be distinguished from cicatricial alopecia.
4
It is unclear whether or not the fibrosis
seen in follicular streamers (stelae or
fibrous tracts) is permanent and/or alters
the downgrowth of anagen hair follicles.
Only 55% of male pattern AGA patients with
microinflammation had hair regrowth in response
to minoxidil treatment, which was less than
the 77% of patients
with no signs of inflammation, 4
suggesting that, to some extent, perifollicular
microinflammation may account for some cases
of male pattern AGA which do not
respond to minoxidil. 4
Another study on 412 patients (193 men
and 219 women) confirmed the presence of
a significant degree of inflammation and
fibrosis in at least 37% of AGA cases. 5
The upper location of the infiltrate
near the infrainfundibulum 2
7 clearly distinguishes AGA from alopecia
areata (AA), the latter disease being characterized
by infiltrates in the bulb and dermal papilla
zone. 12
The
aim of this review is to determine the location
and chronology of the microinflammation
process within the complex pathophysiology
of the human pilosebaceous unit in order
to improve the possible approaches for the
reduction or prevention of the development
of AGA. |
| Classically,
an inflammatory process is ascribed to a
central major mediator or pathway. Such
a monofactorial vision has been historically
well exemplified by the famous interleukin-1
(IL-1) scheme developed by Oppenheim et al
. 13
which is still valid even after 13 years.
In fact, many inflammatory agents are at
the center of a huge array of effects, involving
cells, enzymes, adhesion molecules and other
biological mechanisms. The identification
of the effects of isolated factors is only
part of the problem; it may be more important
to determine when and where the individual
factors are involved in the complex sequence.
This pathway has been clearly identified,
and several inhibitory anti-inflammatory
drugs acting on this aspect of inflammation
have been developed and clinically evaluated.
14,15
, 16,17
|
The
cytokine/chemokine side of microinflammation
Why
does microinflammation take place in the
pilosebaceous unit and for what benefit
and purpose? Fig. 2
and Fig. 3
show, in a simplified sequence, that
inflammation is a multistep process which
may start from a primary event. Let us look
at the clues at the "crime scene" of AGA:
we observe a perifollicular infiltrate in
the upper follicle near the infundibulum.
2
7 This suggests that the primary causal
event for the triggering of inflammation
might occur near the infundibulum. 3,7
Supporting this point of view, improvement
of the inflammatory aspect of AGA has been
reported in a pilot study with an antimicrobial
lotion.
7
One could speculate that several inhabitants
of the scalp, such as the "triad" ( Propionibacterium
sp.; Staphylococcus sp.;
Malassezia ovalis ) or other members
of the transient flora, could be involved
in this complex inflammatory process. 7
The presence of
porphyrins (produced by Propionibacterium
sp.) in the pilosebaceous duct of
58% of AGA patients (compared with 12% of
control subjects), which are able
to induce the production of complement (C5)
chemotactic factor, is considered to be
a possible cofactor of this initial pro-inflammatory
stress. 6,7
Keratinocytes
are also known to respond within minutes
to chemical stress, pollutants, UV irradiation
or even mechanical stress. 37
Not only are radical oxygen species,
38
NO, 39
PGs, and histamine 40
produced, but also intracellularly stored
IL-1 is released 37,41
(see Fig. 2
and step 1 of Fig. 3
). By itself, this pro-inflammatory
cytokine (as well as IL-1 which binds to
the same receptor) is able to inhibit the
growth of isolated hair follicles in culture
in vitro. 9
11 This concentration-dependent inhibition
of human hair elongation and survival indicates
a high sensitivity to IL-1 of the isolated
organ in culture in vitro (IC
50 = 10 pg/mL 11
). In vivo , transgenic mice
which overexpress IL-1 in the basal
epidermis and in the outer root sheath of
their pelage hair follicles exhibit a spontaneous
cutaneous phenotype characterized by a sparseness
of hair. 42
As a response to an IL-1 signal, adjacent
keratinocytes which express receptors for
IL-1 start to engage the transcription of
IL-1 responsive genes 41
( Fig. 3
, step 2). In
vitro , following IL-1 stimulation,
this transcriptional activation cascade
is induced within 6 h in plucked human hair
follicles. 11
Alternatively, skin keratinocytes, which
may also have antigen presenting capabilities,
could theoretically induce T-cell proliferation
in response to bacterial antigens. 51 These
antigens, once they have been "tagged,"
are then selectively destroyed by infiltrating
macrophages, Langerhans cells, or natural
killer cells. 50,52 On many occasions, however,
the causal agent persists, resulting in
sustained inflammation ( Fig. 3, step 4).
This corresponds partly to the situation
which has been pictured in the progression
zone of roughly one-third of alopecia cases:
infiltrating T lymphocytes, together with
mastocytes and macrophages, located in the
upper perifollicular adventitial dermal
sheath perpetuate a local inflammatory stage.
27 This phase of inflammation
often results in tissue remodeling, where
collagenases, such as matrix metalloproteinase
(MMP)-9 (transcriptionally activated by
pro-inflammatory cytokines) or MMP-8 (directly
produced by infiltrating cells), may play
an active role. 5355 Thus, collagenases
are suspected to contribute to the tissue
changes and the so-called "perifollicular
fibrosis" by "preparing"
tissue matrix and basal membranes for macrophages
and T-cell adhesion. Accordingly,
this scenario facilitates the secretion
of membrane-anchored cytokines, such as
TNF-. 55 Other factors, such as MCP-1, have
been directly suspected to contribute to
organ fibrosis in an experimental model
of renal inflammation. 56 As MCP-1, together
with other chemokines, was found to be expressed
in human hair follicles in vitro, 11 as
well as in the eccrine ducts of sebaceous
glands in vivo, 57 it might also be actively
involved in the progression of perifollicular
fibrosis detected in AGA. 26 The development
of perifollicular fibrosis might thus appear
as the signature of a disequilibrium between
pro-and anti-inflammatory pathways.
Relations
between inflammation and steroidogenesis:
the missing link
There is no question that androgens are
major modulators of hair loss. Recently,
it was shown that testosterone inhibited
the growth of outer root sheath keratinocytes
only when they were cocultured with dermal
papilla cells derived from the bald scalp
of an adult macaque, 58 reinforcing the
hypothesis of an androgen influence on hair
growth via the dermal papilla. 59
The potent metabolite of testosterone (i.e.
5-dihydrotestosterone, 5-DHT) is considered
as a "culprit". 60 5-DHT is generated
from testosterone through the activity of
5-reductase (5-R). Two active isoforms of
5-R, which differ both in tissue site distribution
as well as in optimal pH for enzymatic activity,
have been identified and cloned. 61,62,
63 While the type II isoform is considered
to be the major isozyme in genital tissues,
61 the type I isoform is considered to be
the major isoform expressed in skin and
in the pilosebaceous unit. 64,65 Isoform
II, however, has recently been detected
in the inner root sheath of the pilosebaceous
unit by immunohistochemistry, 66,67 Northern
blotting, 67 and the pH dependence of optimal
enzymatic activity. 67 Thus, the contribution
of both isoforms in the regression of the
pilosebaceous unit is still a matter of
debate. Recently, a clinical study using
finasteride, a strong inhibitor of 5-RII
(and weak inhibitor of 5-RI), showed that
intervention in androgen metabolism could,
to some extent, modulate the progression
of AGA, when the drug was given by the oral
route, 68 but not topically. 69 After oral
ingestion, an improvement of hair growth
was observed, which was associated with
a drastic reduction of serum levels of 5-DHT,
corresponding to those observed in castrates.
68 Despite such a
reduction of circulating 5-DHT levels, however,
a number of individuals (60-70%) still remained
unresponsive to this treatment, indicating
again that simple dysregulation of 5-DHT
synthesis levels or a genetic polymorphism
of 5-R genes cannot account for all cases
of AGA, and a polygenic etiology should
be considered. 1
Thus,
to date, the only evident link that can
be established between androgen metabolism
and the complex inflammatory process is
sebum production which is controlled by
androgens.
70 As sebum harbors a large amount of microorganisms
which use lipids as nutrients, 8 it cannot
be excluded that, at least for some individuals,
androgen metabolism might facilitate the
colonization of the sebaceous infundibulum
and sebaceous ducts by such microorganisms
which may be involved in the first steps
of pilosebaceous unit inflammation.
We propose here working
hypotheses which do not invalidate the contribution
of a hereditary genetic androgen imbalance
in AGA, 60 but rather attempt to integrate
the neglected microinflammatory aspects
of alopecia into the complex etiology of
AGA. On the one hand, excessive local
and/or endocrine, genetically exacerbated
5-DHT synthesis results in sebaceous
gland enlargement; 2,60 as a consequence,
some scalps might
offer more comfortable niches to harbor
the previously mentioned pro-inflammatory
microorganisms. 6,7 On the other
hand, androgen imbalance and metabolism
may be locally exacerbated by pro-inflammatory
cytokines. For example, gingival fibroblasts
have been reported to modify their androgen
metabolism through the action of several
growth factors, such as epidermal growth
factor (EGF), transforming growth factor
beta (TGF-), and the pro-inflammatory cytokines
IL-1 and TNF-. 71 Therefore, one could speculate
that, once the inflammatory
process has been triggered, the androgenetic
mechanism of alopecia could subsequently
be locally amplified. This upregulation
of androgen metabolism by pro-inflammatory
cytokines remains, however, to be established
at the pilosebaceous unit level.
| Our
visit to the "crime scene" of AGA
yielded many clues ( Fig. 4
). We know now that, at least
in about one-third
of cases, the tool which causes the
lethal damage is a microinflammatory
process. Several factors are
present, however, which are suspected
to have handled the tool: androgens,
microbial flora, endogenous or exogenous
stress, genetic imbalance, and possibly
others. Although other suspects or
tools are likely to be discovered
in the future, it cannot be excluded
that, for each individual, the causal
agent, as well as the sequence of
events or combined factors, may be
different. The large number of molecules
claimed to be active and patented
in this field, 89
and their limited efficacy in
offering a definite and extensive
cure of AGA, confirm that the mechanism
of AGA is highly complex. Accordingly,
it appears that, due to the complexity
and multiple interactivities and cooperations
involved throughout the distinct inflammatory
pathways (partly described in Fig. 2
), an anti-inflammatory strategy
should be targeted to the appropriate
effector(s) at the right moment. For
this purpose, we have developed a
simple assay to evaluate individuals
with potentially affected hair follicles.
11
We observed that plucked hair
specimens of 33% of the 116 volunteers
evaluated could be classified as highly
inflammatory in terms of spontaneous
IL-1 production. 11
Consequently, the identification
of the "inflammatory alopecic individuals"
may help to adapt the right answer
to
the right cause. Such a selective
approach might be valuable for other
parameters, such as an imbalance in
11 HSD activity, 5-DHT synthesis,
or microorganism colonization. Encompassing
individual diversity is thus a prerequisite
for appropriately addressing the biological
conditions contributing to AGA. Our
findings and a review of the literature
suggest that inflammation in its diversity
is a potentially active player to
consider in this approach. |