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

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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.

Dermatol Surg 2002 Sep;28(9):804-7

A random study of Asian male androgenetic alopecia in Bangkok, Thailand.

BACKGROUND: Androgenetic alopecia remains the most common cause of male pattern baldness (MPB) in all races. The prevalence of MPB in Caucasians is well documented. The prevalence of MPB in Asians is believed to be very low, only one-fourth to one-third on average compared to Caucasians. However, according to my previous study, there is a clear trend indicating that it is approaching that of Caucasians. OBJECTIVE: To assess the prevalence of MPB in the Asian population in Bangkok, Thailand; to compare this prevalence to previous studies conducted on Asians; and to compare the results to previous studies conducted on Caucasian. METHODS: This study was conducted by two physicians and assisted by two registered nurses. The questionnaire included age, sex, Norwood classification, diet, family history of baldness, income, and education. The physicians examined the scalp of each interviewee upon completion of each questionnaire. The ethnic focus group in this study was Thai and Chinese who reside in Bangkok, Thailand. The interviews were conducted in hospitals, nursing homes, classroom, medical meetings, temples, parks, and villages. RESULTS: A total of 1124 men were randomized in this study. The prevalence of cosmetically significant MPB (Norwood III-VII) was 38.52% and steadily increasing with age, approaching that of Caucasians. Variant MPB was found to be 0.67% and other types of androgenetic alopecia was 0.6%. From an ethnic point of view, the majority of the groups were of mixed blood and mostly of Chinese origin, thus we were unable to distinguish between Chinese and Thai. CONCLUSION: This study shows that the prevalence of MPB in Asians is not as low as previously thought. The cause of this increasing prevalence is uncertain. There are no past studies in Thailand for comparison, however, it can be extrapolated that the socioeconomic environment and westernized diet may contribute to this prevalence.

J Dermatol 2002 Apr;29(4):197-201

Ultrastructural study of acquired pili torti-like hair defects accompanying pseudopelade.

Acquired structural hair defects are caused by various physical and chemical manipulations. Plucked hairs and hair follicle biopsy specimens of pili torti-like hairs that arose from pseudopelade scalp were studied. In scanning electron microscopy, the hair shafts had a segmental pili torti-like appearance, accompanied by oblique or longitudinal grooves and ridges. In light microscopy, the hair follicles showed an asymmetric hair bulb and inner root sheath, and a shortened keratogenous zone within sclerosing fibrous connective tissue. In transmission electron microscopy, the numbers and thickness of the hair cuticle cells were different on the opposite sides of the hair shaft. The hair cuticle was irregularly shaped and formed asymmetric waves. The tonofilaments in the hair cortex ran almost parallel to the hair axis. From these findings, it was clear that the grooves and ridges were produced by the deformed hair cuticle and cortex, whose shapes were modulated by the asymmetric inner root sheath. This asymmetry most likely resulted from a dysfunctional dermal papilla, which was affected by fibrosis. The pili torti-like appearance appeared to be caused by the grooves and ridges that ran obliquely on the hair shaft surface.

Am J Clin Dermatol. 2003;4(6):371-8.

Skin aging and menopause : implications for treatment.

The skin is one of the largest organs of the body, which is significantly affected by the aging process and menopause. The significant changes sustained by the skin during the menopause are due to the effect sustained on the skin's individual components.The estrogen receptor has been detected on the cellular components of the skin. Accordingly, dermal cellular metabolism is influenced by the hypoestrogenoemic state of menopause leading to changes in the collagen content, alterations in the concentration of glycoaminoglycans and most importantly the water content. Consequently changes in these basic components leads to an alteration in function compatible with skin aging.Changes in the skin collagen leads to diminished elasticity and skin strength. Collagen content may be measured by various methods such as direct skin biopsy, skin blister assessment for collagen markers and skin thickness measurement. All these variables indicate a reduction in collagen content following menopause. This may be reversed with the administration of estrogen given both topically and systemically.A reduction in hydrophilic glycoaminglycans leads to a direct reduction in water content, which influences the skin turgor. These effects on glycoaminoglycans, due to the hypoestrogenia, have been clearly shown in animal studies and appeared to be rapidly reversed with the application of estrogens. The sum total of these basic effects on the skin leads to wrinkles, the skin condition typifying skin aging.Structures resident in the skin are likewise influenced by menopause. Changes to the cutaneous vascular reactivity are noted following menopause. Capillary blood flow velocity decreases significantly in postmenopausal women. Postmenopausal flushing is due to profound vasodilatation in the dermal papillae. Hair growth is also influenced by the hormonal milieu and consequently hair loss has been associated with the beginning of menopause.Treatments administered for menopause, in particular hormone replacement therapy, appear to alter its effects on the basic components of the skin as well as the more complex structures residing in the skin, consequently retarding the skin aging process.

Being such a complex biological process, hair growth biology is still a work in progress. Noetheless, several therapeutic methods, including drugs, surgery, and suppelements have been in use to help those who attempt to restore their hair. None of these approaches are perfect due to the diversity in the causes underlying hair loss. Also, most of chemical drugs and hair transplantation surgeries are accompanied by undesirable side effects.

DreamPharm offers Hair Million to address hair loss problems. Numerous anecdotal cases have demonstrated that this herbal formula based on authentic Chinese herbs actually improves the age-related hair thinning and hair loss among a significant fraction of people who take it regularly. We still do not understand the mechanisms of action as to how Hair Million works to stop hair loss and promote hair growth, despite all the positive anecdotal observations. Neither scientific research nor placebo controlled clinical analysis has been conducted because it will cost dearly. Lack of scientific/clinical research is quite common in herbal arena. Just because science hasn't scrutinized we should not stop taking daily food and herbal supplements altogether: our life must go on until we have better understandings of food and herb. There are two merits in this hair restoration herbal formula: Firstly, Hair Million is relatively inexpensive, and secondly, it is made of edible herbs that are known to be safe when consumed in regular quantities. For scientifically proven prescription medication, check Propecia.

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