Biology
of hair
Abstract
The hair and nails develop
through evolutionarily conserved mechanisms. They have a range of shared
features, as both represent adnexal structures with specialized keratin
constituents characterized by low water content and high sulfur content.
However, the hair follicle cycles continuously, while the nail exhibits
uninterrupted growth. Hair and nails serve multiple functions, including protection,
sensation, and social communication. The hair follicle is a site of immune
privilege and a major reservoir for epithelial and melanocyte stem cells;
immune privilege and stem cells within the nail unit are also becoming
recognized. The hair cycle includes phases of growth (anagen), regression
(catagen), resting (telogen), and hair shaft shedding (exogen/teloptosis). The
nail apparatus consists of the fully cornified nail plate, which is produced by
the nail matrix, and other specialized epithelial tissues such as the nail bed
and nail folds.
Hair follicles are remarkably productive
organs that undergo constant tissue remodeling. During its cyclic
transformation, the hair follicle changes from a phase of rapid growth (anagen)
to a resting period (telogen) via apoptosis-driven regression (catagen). Anagen
is the phase of massive and rapid tissue transformation of the lower follicle.
It can be divided in seven stages: (1) growth of the dermal papilla and onset
of mitotic activity in the overlying epithelial cells; (2) envelopment of the
dermal papilla by bulb matrix cells and early differentiation; (3) full
differentiation of bulb matrix cells into all follicular components; (4)
reactivation of matrix melanocytes; (5) emergence of the hair shaft and
dislodging of the old telogen hair in the dermis; (6) emergence of the new hair
shaft from the skin surface; and (7) stable growth.
Hair follicles undergo cyclic transformation.
Rapid growth (anagen) is followed by resting period (telogen) via apoptosis-driven
regression (catagen).
The length of the anagen phase varies
depending on the body site. Terminal hairs on the scalp show an anagen phase of
approximately 3–6 years. Catagen is marked by an extensive destruction of the
lower follicle. Matrix and lower outer root sheath cell stop proliferating
abruptly and undergo apoptosis. Melanocytes stop producing pigment before the
matrix cell proliferation stops, which leads to an unpigmented proximal end of
the telogen hair. This transitional period lasts 2–4 weeks. Once the involution
of catagen is complete and a club hair is formed, the follicle has entered
telogen and has lost one third of its original length. The dermal papilla has
disintegrated, except for a few cells; the inner root sheath is gone. The
distal outer root sheath closes around the fully keratinized hair shaft. The
telogen phase of terminal scalp hair lasts around 3 months on the scalp. It is
followed by the shedding of the hair shaft, called exogen. Normally up to 90%
of the hair follicles are in anagen while, around 10% are in telogen and 1%–2%
in catagen.
A hair follicle can functionally and
anatomically be divided in four compartments: (1) infundibulum, (2) isthmus,
(3) suprabulbar, and (4) bulb region.
The infundibulum extends from the epidermis
to the opening of the excretory duct of the sebaceous gland. The epithelium of
the infundibulum is continuous with the epidermis and shows a similar
appearance; its cells seem to have a higher proliferative capacity and they can
regenerate the epidermis after wounding or injury. The infundibulum is formed
like a funnel; its lumen normally contains the hair shaft, keratin material and
sebum, and sometimes, apocrine secretion (pubic hair), lipophilic yeast, and
Demodex mites (sebaceous follicles on the face).
The hair follicle can be divided in 4
compartments: infundibulum, isthmus, suprabulbar and bulb region.
The isthmus extends from the opening of the
sebaceous duct to the insertion of the arrector pili muscle. The outer root
sheath of the isthmus, in contrast to the interfollicular epidermis, has no
granular layer and its cells contain an increased amount of glycogen. Above the
insertion of the arrector pili muscle, the inner root sheath of a growing
(anagen) hair follicle disintegrates. From this point to the opening of the
sebaceous gland, the outer root sheath shows a special type of keratinization,
called trichilemmal keratinization. The inferior part of the isthmus, at the
point of the insertion of the arrector pili muscle, is called the bulge are.
The bulge is composed of biochemically distinctive keratinocytes that posses
the characteristics of epithelial stem cells.
The suprabulbar region undergoes dramatic
changes during hair cycling. It extends from the bulge area to the hair bulb.
In growing hair follicles (anagen) it is comprised of three layers: (1) the
outer root sheath, (2) inner root sheath, and (3) hair shaft. The inner root
sheath is fully keratinized and its innermost cuticle cells interlock with the
cuticle cells of the hair shaft, which therefore is tightly anchored in the
skin during anagen.
The bulb is the deep, bulbous portion of the
follicle that surrounds the dermal papilla. The bulb contains the matrix
keratinocytes, which rapidly proliferate to generate the hair shaft. This rate
of proliferation is one of the highest of any tissue in the body. Therefore, it
is not surprising that these epithelial cells are exquisitely vulnerable and
sensitive to any kind of internal and external influences like stress, drugs,
hormones and immunologic or physical injury.
Hair matrix keratinocytes undergo terminal
differentiation while being infused with melanin granules produced by
specialized melanocytes of the hair follicle pigmentary unit. Two different
types of melanin can be distinguished: (1) eumelanin, which is brown or black,
and (2) pheomelanin, which is yellow or red. Differences in hair color are not
a result of the number of melanocytes. Rather, they are largely the result of
differences in the amount and types of melanin produced and the macromolecular
structure and packaging of melanin. Furthermore, hair color may vary both in
time and site. For example, scalp hair may be blonde in childhood and become
brown or black in adolescence, before becoming white again in middle or old
age; beard or pubic hair may be red and the scalp hair black or dark brown in
the same individual.
Hair follicle formation starts in utero
during the 12th and 15th week of pregnancy. By week 22, hair follicle formation
is completed and the fetus is covered with downy, lightly pigmented,
nonmedullated hair, called lanugo hair, which grows up to a length of 2–3 cm.
This hair shows a synchronous hair cycle and grows in two phases. The first
lanugo hair is shed in the 7th–8th month of pregnancy, the second set of lanugo
hair is shed by the time of birth up to 3 months of age. After that, hair
follicles produce fine, nonmedullated vellus hair that only grows a few mm long.
After lanugo hairs are shed, the growth cycle is asynchronous, meaning that
each follicle develops its own cycle and the hair does not fall out at the same
time. Hair follicles on the scalp produce a pigmented, thicker, longer hair
type, which is not fully medullated at the time of birth. By age 2, thick,
completely medullated terminal hairs replace these hairs. Terminal hair on the
scalp shows an anagen phase of around 3–6 years. Not every hair follicle on the
scalp produces terminal hairs. The ratio of terminal to vellus hair (T: V)
ranges from 1.7:1 to 6.0:1.
Structure
of the hair fiber
In
response to signals from the dermal papilla, the matrix cells at the base of
the follicle proliferate and differentiate during anagen, forming the layers of
the follicle. The three central lineages – medulla, cortex, and hair cuticle –
form the hair fiber, which fulfills the primary hair-producing function of the
anagen follicle. Surrounding the hair fiber are the three concentric layers
that compose the inner root sheath (IRS): the IRS cuticle, Huxley’s layer, and
Henle’s layer. The IRS undergoes a complex program of differentiation during
anagen, with Henle’s layer terminally differentiating shortly after formation.
The IRS cuticle differentiates further up the follicle, followed by Huxley’s
layer; all three layers undergo desmosomal remodeling during terminal
differentiation. The IRS forms a mechanically supportive tube around the hair
fiber and is degraded by proteolytic enzymes at the level of the isthmus, allowing
the hair shaft to enter the hair canal and emerge from the skin surface.
Heparanase expressed in the IRS during anagen acts on heparin sulfate
proteoglycans and controls IRS differentiation by influencing growth factor
sequestration and diffusion.
The
seventh concentric layer that originates from the matrix in line with the hair
fiber and IRS is the companion layer, which is a single cell thick. Regarded as
the “slippage plane” between the IRS and the surrounding ORS during anagen, the
companion layer enables directional hair growth. It is attached to the IRS
through “Flugelzellen” structures that extend from Huxley’s layer through
Henle’s layer and link to the companion layer via numerous desmosomes. A
“barrel” of transversely oriented intermediate filaments on the inner side of
the companion layer are thought to provide support for the inner root sheath,
protecting it from the compressive forces of the expanding ORS.
