Infundibular protein and RNA microarray analyses from affected and clinically non-affected scalp in male androgenetic alopecia patients

Androgenetic alopecia (AGA) is one of the most common chronic problems seen by dermatologists worldwide. It is characterized by progressive hair loss, especially of scalp hair, and has distinctive patterns of loss in women versus men, but in both genders the central scalp is most severely affected. It often begins around puberty and is known to effect self-esteem and the individual's quality of life. In contrast to the high prevalence of AGA, approved therapeutic options are limited. In addition to the scarce pharmacologic treatments, there are numerous nonprescription products claimed to be effective in restoring hair in androgenetic alopecia.

Most common forms of hair loss (alopecia) are caused by aberrant hair follicle cycling and changes in hair follicle morphology. However, current treatments for alopecia do not specifically target these processes. We are now beginning to identify the molecules and molecular pathways that control normal hair follicle formation, cycling and growth. In parallel, new techniques are being developed for delivering molecules to hair follicles. Here, we outline the characteristics of common hair loss diseases, and discuss ways in which recent advances in hair follicle biology could be translated into effective therapies for these conditions.

The hair follicle (HF) represents a prototypic ectodermal-mesodermal interaction system in which central questions of modern biology can be studied. A unique feature of these stem-cell-rich mini-organs is that they undergo life-long, cyclic transformations between stages of active regeneration (anagen), apoptotic involution (catagen), and relative proliferative quiescence (telogen). Due to the low proliferation rate and small size of the HF during telogen, this stage was conventionally thought of as a stage of dormancy. However, multiple lines of newly emerging evidence show that HFs during telogen are anything but dormant. Here, we emphasize that telogen is a highly energy-efficient default state of the mammalian coat, whose function centres around maintenance of the hair fibre and prompt responses to its loss. While actively retaining hair fibres with minimal energy expenditure, telogen HFs can launch a new regeneration cycle in response to a variety of stimuli originating in their autonomous micro-environment (including its stem cell niche) as well as in their external tissue macro-environment. Regenerative responses of telogen HFs change as a function of time and can be divided into two sub-stages: early 'refractory' and late 'competent' telogen. These changing activities are reflected in hundreds of dynamically regulated genes in telogen skin, possibly aimed at establishing a fast response-signalling environment to trauma and other disturbances of skin homeostasis. Furthermore, telogen is an interpreter of circadian output in the timing of anagen initiation and the key stage during which the subsequent organ regeneration (anagen) is actively prepared by suppressing molecular brakes on hair growth while activating pro-regenerative signals. Thus, telogen may serve as an excellent model system for dissecting signalling and cellular interactions that precede the active 'regenerative mode' of tissue remodeling. This revised understanding of telogen biology also points to intriguing new therapeutic avenues in the management of common human hair growth disorders.