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Curr Biol 2003 Feb 18;13(4):333-8

Notch/RBP-J Signaling Regulates Epidermis/Hair Fate Determination of Hair Follicular Stem Cells.


Notch signaling is involved in the cell fate determination of various cell lineages. Notch interaction with its ligand induces the cleavage of its intracellular domain (IC), and the Notch IC translocates to the nucleus and binds to RBP-J to transactivate transcription of target genes. All four Notches in mammals bind to RBP-J to exert their transactivation activities. Notch is expressed in developing or differentiating epidermis and hairs, inhibits the terminal differentiation of the epidermis, and regulates hair differentiation. The common stem cells that reside in the upper portion of hair follicles (the bulge) contribute to epidermal and hair cell formation. However, it is unknown what determines whether hair follicular stem cells will become hairs or epidermis. Here we report that conditionally disrupting the mouse RBP-J gene in a mosaic pattern to avoid embryonic lethality of RBP-J-deficiency caused hair loss, epidermal hyperkeratinization, and epidermal cyst formation. Cyst formation is probably due to a combination of the aberrant fate determination of RBP-J-deficient stem cells to epidermal progenitors and their accelerated differentiation into epidermis. These results suggest that Notch/RBP-J signaling regulates the cell fate determination of hair follicular stem cells at the bulge region.


J Invest Dermatol 2003 Jan;120(1):27-35

Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss.


Chemotherapy alters the structure and function of hair follicle melanocytes. Molecular mechanisms controlling melanocyte responses during chemotherapy-induced hair loss, however, remain largely unknown. Using immunohistology and multicolor confocal microscopy, we show here that cyclophosphamide administration to C57BL/6 mice alters the activity and fate of hair follicle melanocytes. After 24-48 h, hair bulb melanocytes expressing Fas undergo apoptosis. The number of apoptotic follicular melanocytes is significantly reduced (p<0.01) in cyclophosphamide-treated Fas knockout mice compared to wild-type controls, suggesting that Fas signaling contributes to chemotherapy-induced melanocyte death. After 3-5 d, surviving hair bulb melanocytes express c-kit receptor, proliferate, and appear to migrate up the outer root sheath. Tyrosinase-positive and melanogenically active cells then appear in the epidermis. By Western blotting and immunohistochemistry, expression levels of the c-kit ligand, stem cell factor, in skin and epidermis are strongly increased after cyclophosphamide treatment. Cyclophosphamide-induced migration of the hair follicle melanocytes into epidermis is completely abrogated by administration of c-kit neutralizing antibody. These data suggest that chemotherapy induces a complex response in the hair follicle melanocytes, which includes apoptosis, proliferation, and migration. Pharmacologic manipulation of Fas and c-kit signaling pathways might be useful for the correction of skin hyperpigmentation as a side-effect of chemotherapy.


J Dermatol 2002 Oct;29(10):665-9

Depression circumstantially related to the administration of finasteride for androgenetic alopecia.


In this paper we report 19 patients (14 males, 5 females; mean age 28.16 years +/- 7.68 SD) out of a series of 23 (17 males, 5 females) who developed a mood disturbance (moderate to severe depression) during treatment with finasteride, 1 mg/day orally, for androgenetic alopecia (Hamilton subtypes III-V; Ludwig subtypes I-II). Depression, which significatively impaired sociofamilial relations, sleep and eating behaviour, was associated to marked anxiety in some cases, developed after 9-19 weeks of treatment with finasteride, and promptly resolved after suspension of the drug. Two patients accepted reintroduction of the drug, and depression relapsed within 2 weeks. Depression as an adverse effect of finasteride has been reported only once. Further studies are needed to confirm our circumstantial observations, which are based on a retrospective series of patients.


J Cardiovasc Risk. 2003 Jun;10(3):227-31.

Hair loss, insulin resistance, and heredity in middle-aged women. A population-based study.

CONTEXTThe association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented.OBJECTIVES AND DESIGNThe aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998.SETTING AND PARTICIPANTSAs a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion.RESULTSThe prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models.CONCLUSIONSAccording to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.


Hair growth is a sophisticated biological process, which is still not thoroughly understood. A multitude of therapeutic measures, including drugs, surgery, and suppelements have been made available, and used. However, due to the diversity of the problems underlying hair loss, there is no single solution for all hair loss cases. Most of chemical drugs and hair transplantation surgeries are not free from varying degrees of undesirable side effects on health.

Hair Million is an alternative solution to hair loss problems. Anecdotally, it shows prositive results and improvement especially for age-related hair thinning and hair loss for a fraction of people who take it. We do not know the mechanisms of action as to how Hair Million works to help stop hair loss, and promote hair growth. We only know by anecdotal observations. There has been no clinical trials nor placebo controlled statistical analysis on the efficacy of Hair Million on hair loss and hair growth. For the clinically tested, FDA approved prescription medication, check Propecia.







Related Web resources:


  • What is hair?
  • Curly Hair
  • Biology of hair growth and development.
  • The phenomenon of hair loss.
  • Methods and treatments for hair loss and baldness.
  • Drugs and hair transplantation surgery for hair loss and baldness.
  • Hair loss linked to other health problems.
  • Baldness by choice and fashion.
  • Alopecia info.
  • Alopecia treatment info.
  • Alopecia treatment info.
  • Hair care info.
  • Hair loss and alopecia research articles: abstracts and source links.



    DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.





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