HAIR LOSS AND REGROWTH
http://www.ehrs.org/conferenceabstracts/2004berlin/guestlectures/B2-5-Sim.htm
B2.5 TESTOSTERONE TO EPITESTOSTERONE RATIO IN MALE PATTERN BALDNESS
Woo-Young Sim, Hyo-Jung Bang1, Bong Chul Chung1
Department of Dermatology, College of Medicine, Kyung Hee University, Bioanalysis and Biotransformation Research Center, KIST1, Seoul, Korea
It is generally accepted that male pattern baldness (MPB) is a direct consequence of both androgenic stimulation and genetic predisposition. Although the pathogenesis of MPB is not well understood, it may be determined by an increase of 5 alpha-reductase. Epitestosterone, a natural epimer of testosterone, is a physiological constituent of body fluids in many species, including man. It was demonstrated that epitestosterone inhibited the androgenic effect by competition with testosterone.
The level of dihydrotestosterone (DHT), testosterone and epitestosterone in hairs of premature baldness subjects and non-baldness subjects was evaluated by gas chromatography-mass spectrometry in selected ion monitoring mode. The ratio of testosterone to epitestosterone (T/E ratio) and DHT level in vertex hair of premature baldness were higher than the value of non-baldness subjects. However, the level of androgen in occipital hair of same baldness group was not different. The T/E ratio in hairs from advanced baldness was much higher than that of premature baldness in our previous study. These findings demonstrated that the T/E ratio might be used as indicator for MPB.
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http://www.arclab.org/medlineupdates/abstract_11994368.htmlSex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects.
- Havlikova H, Hill M, Hampl R, Starka L
J Clin Endocrinol Metab 2002 May;87(5):2225-31.Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor pregnenolone sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with pregnenolone sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty occurred. In conclusion, concentrations of epitestosterone and pregnenolone sulfate are age dependent and, at least in prepubertal boys and girls, epitestosterone reaches or even exceeds the concentrations of T, thus supporting its role as an endogenous antiandrogen. The dissimilarities in the course of epitestosterone levels through the lifespan of men and women and its relation to pregnenolone sulfate concentrations raise the question of the contribution of the adrenals and gonads to the production of both steroids and even to the uniformity of the mechanism of epitestosterone formation.
---------------------------------------------------------------------Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp.
Bayne EK, Flanagan J, Einstein M, Ayala J, Chang B, Azzolina B, Whiting DA, Mumford RA, Thiboutot D, Singer II, Harris G.
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. ellen_bayne@merck.com
The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin-biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle.
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Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent.
Kamimura A, Takahashi T, Watanabe Y.
Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Ibaraki, Japan. ayako.kamimura@kyowa.co.jp
Procyanidin B-2 is a polyphenol compound we have identified in apple which acts as a hair-growing factor in the murine model both in vitro and in vivo. This report describes our investigation of the effects of 1% procyanidin B-2 tonic on human hair growth after sequential use for 6 months. A double-blind clinical test involving a total of 29 subjects was performed. Nineteen men in the procyanidin B-2 group and 10 men in the placebo control group were subjected to analyses. No adverse side effects were observed in either group. The hair-growing effect was evaluated using a macrophotography technique combined with measurements of the hair diameter of clipped hairs. The increase in number of total hairs in the designated scalp area (0.5 cm square = 0.25 cm2 area) of procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 6.68 +/- 5.53 (mean +/- SD)/0.25 cm2; placebo, 0.08 +/- 4.56 (mean +/- SD)/0.25 cm2; P < 0.005, two-sample t test). The increase in number of terminal hairs, which are defined as hairs more than 60 microm in diameter, in the designated area (0.5 cm square = 0.25 cm2 area) of the procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 1.99 +/- 2.58 (mean +/- SD)/0.25 cm2; placebo, -0.82 +/- 3.40 (mean +/- SD)/0.25 cm2; P < 0.02, two-sample t test). Procyanidin B-2 therapy shows potential as a safe and promising cure for male pattern baldness.
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Hair growth induction by the tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression.
Sredni B, Gal R, Cohen IJ, Dazard JE, Givol D, Gafter U, Motro B, Eliyahu S, Albeck M, Lander HM, Kalechman Y.
The synthetic immunomodulator AS101{ammonium trichloro(dioxoethylene-o,o')tellurate} was previously found to protect cancer patients from chemotherapy-induced bone marrow toxicity and alopecia. Here we show that AS101 induces hair growth in nude and normal mice. AS101 possesses the dual ability to both induce anagen and retard spontaneous catagen in the C57BL/6 mouse model. Anagen induced by AS101 is mediated by keratinocyte growth factor (KGF), as it is abrogated both in nude mice co-treated with AS101 plus neutralizing anti KGF antibodies and in AS101-treated transgenic mice expressing a dominant-negative KGF receptor transgene in basal keratinocytes. AS101 up-regulates KGF expression by activating the ras signaling pathway in cultured fibroblasts. AS101-induced delayed catagen is associated with inhibition of terminal differentiation marker expression both in nude and C57BL/6 mice epidermal follicular keratinocytes and in cultures of primary mouse follicular keratinocytes induced to differentiate. This activity is associated with relatively sustained elevation of p21waf. Delayed expression of terminal differentiation markers was not induced by AS101 in follicular keratinocytes from p21waf knockout mice. Because similar results were obtained with cultures of primary human keratinocytes and fibroblasts, preliminary case report studies revealed substantial hair growth when AS101 was topically applied on three adolescents who had remained alopeciac 1-2 years after chemotherapy. The results emphasize the unique mode of action of AS101 and highlight its potential clinical use for treating certain types of alopecia.
--------------------------------------------------------------------------------------Prostaglandin-induced hair growth.
Johnstone MA, Albert DM.
Glaucoma Consultants Northwest, Swedish Medical Center, Seattle, WA 98104, USA.
Latanoprost, used clinically in the treatment of glaucoma, induces growth of lashes and ancillary hairs around the eyelids. Manifestations include greater thickness and length of lashes, additional lash rows, conversion of vellus to terminal hairs in canthal areas as well as in regions adjacent to lash rows. In conjunction with increased growth, increased pigmentation occurs. Vellus hairs of the lower eyelids also undergo increased growth and pigmentation. Brief latanoprost therapy for 2-17 days (3-25.5 microg total dosage) induced findings comparable to chronic therapy in five patients. Latanoprost reversed alopecia of the eyelashes in one patient. Laboratory experiments with latanoprost have demonstrated stimulation of hair growth in mice and in the balding scalp of the stumptailed macaque, a primate that demonstrates androgenetic alopecia. The increased number of visible lashes is consistent with the ability of latanoprost to induce anagen (the growth phase) in telogen (resting) follicles while inducing hypertrophic changes in the involved follicles. The increased length of lashes is consistent with the ability of latanoprost to prolong the anagen phase of the hair cycle. Correlation with laboratory studies suggests that initiation and completion of latanoprost hair growth effects occur very early in anagen and the likely target is the dermal papilla.