Andrew G. Messenger

Minoxidil: mechanisms of action on hair growth

We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.

The culture of dermal papilla cells from human hair follicles

Dermal papillae were isolated from human hair follicles and primary cell cultures were established from the papilla explants. The cultured papilla cells spread slowly, initially as a monolayer, and eventually formed multi‐layered parallel arrays of fibroblast‐like cells. At the edges of expanding colonies the cells were large and flattened and showed a tendency to form clumps. The behaviour of human dermal papilla cells in culture is very similar to that reported in cultures of papilla cells from rat vibrissa follicles.

Hair density, hair diameter and the prevalence of female pattern hair loss

Background Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated.

Guidelines for the management of alopecia areata

These guidelines for management of alopecia areata have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence‐based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5′ UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34–amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.

Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin.

Abstract: Oestrogens play a major role in non‐classic target tissues in both sexes, yet there have been few studies on estrogens and skin. Recently a second oestrogen receptor (ERβ) has been discovered. Therefore, we have compared the expression of oestrogen receptor alpha (ERα), beta (ERβ), the androgen receptor (AR) and a cell proliferation marker in male and female non‐balding scalp skin. ERβ was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERα and AR. In the hair follicle, ERβ expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERα, and the AR, which was only expressed in dermal papilla cells. Serial sections also showed strong nuclear expression of ERβ in the cells of the bulge, while neither ERα nor AR was expressed. In the sebaceous gland, ERβ was expressed in both basal and partially differentiated sebocytes. ERα exhibited a similar pattern of expression, while the AR was expressed in the basal and very early differentiated sebocytes. There was no obvious difference in the expression of either oestrogen receptor in male or female skin. The wide distribution of ERβ in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non‐classic target tissues. The differential expression of ERα, ERβ and AR in human skin suggests that the mechanisms by which steroid hormones mediate their effects may be more complex than previously thought.

Why Some Women Look Young for Their Age

The desire of many to look young for their age has led to the establishment of a large cosmetics industry. However, the features of appearance that primarily determine how old women look for their age and whether genetic or environmental factors predominately influence such features are largely unknown. We studied the facial appearance of 102 pairs of female Danish twins aged 59 to 81 as well as 162 British females aged 45 to 75. Skin wrinkling, hair graying and lip height were significantly and independently associated with how old the women looked for their age. The appearance of facial sun-damage was also found to be significantly correlated to how old women look for their age and was primarily due to its commonality with the appearance of skin wrinkles. There was also considerable variation in the perceived age data that was unaccounted for. Composite facial images created from women who looked young or old for their age indicated that the structure of subcutaneous tissue was partly responsible. Heritability analyses of the appearance features revealed that perceived age, pigmented age spots, skin wrinkles and the appearance of sun-damage were influenced more or less equally by genetic and environmental factors. Hair graying, recession of hair from the forehead and lip height were influenced mainly by genetic factors whereas environmental factors influenced hair thinning. These findings indicate that women who look young for their age have large lips, avoid sun-exposure and possess genetic factors that protect against the development of gray hair and skin wrinkles. The findings also demonstrate that perceived age is a better biomarker of skin, hair and facial aging than chronological age.

British Association of Dermatologists' guidelines for the management of alopecia areata 2012

The guidelines have been revised and updated in accordance with a predetermined scope, based on that used in the 2003 guidelines. Recommendations in these guidelines supersede those in the 2003 guidelines. The objectives of the guidelines are to provide up-to-date recommendations for the manage- ment of alopecia areata in adults and children and a summary of the evidence base.Rosalind.Woodworth@utas.edu.au

Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men

Androgenetic alopecia is the most common hair loss disorder, affecting both men and women. Initial signs of androgenetic alopecia usually develop during teenage years leading to progressive hair loss with a pattern distribution. Moreover, its frequency increases with age and affects up to 80 % Caucasian men and 42 % of women.

Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology

A histopathological study was performed in 17 patients with alopecia areata to elucidate the changes in hair cycle dynamics. The findings confirm the view that the initial event in alopecia areata is the premature entry of anagen follicles into telogen, although some follicles survive for a time in a dystrophic anagen state. However, after re‐entry into anagen takes place, growth appears to be halted in anagen III rather than anagen IV, as has previously been suggested. Follicles then return prematurely to telogen and these truncated cycles are repeated until the disease activity subsides. A new pathogenic hypothesis is presented which relates alterations in hair cycle dynamics to pathological changes within the anagen follicle and also provides an explanation for the formation of exclamation mark hairs and the non‐destructive nature of the disease.