Anatomy of the Hair Follicle
Introductory article
This is intended as a short introductory/reference article for further topics on hair biology.
Hair is found everywhere on the body except for the glabrous (non-hairy) skin surfaces - palms of the hands, soles of the feet, lips, and ears. Until puberty all hair is “vellus” hair, colourless and barely visible. The structure of the hair follicle (HF) can be divided into the upper and the lower parts. The upper part includes the infundibulum and isthmus, and the lower part is referred to as the bulb and suprabulbar region. The hair bulb is built by the dermal papilla (which includes a group of specialized fibroblasts, blood capillaries, and nerve endings) and the hair matrix (consisting of rapidly proliferating keratinocytes).
HF’s possess a unique ability in mammalian tissue of being able to regenerate via the HF cycle, and even directly participate in cutaneous wound healing. The HF cycle is divided into four phases: anagen (“growth”), catagen (“transition”), telogen (“resting”) and exogen (“shedding”).
Anagen: HF undergoes rapid, energy-consuming growth and active generation of a pigmented hair fiber.
Catagen: apoptosis-driven organ regression.
Telogen: periods of relative ‘quiescence’, although even during this phase there is intense activity during which the HF prepares itself for the onset of the next anagen cycle.
Exogen: hair shaft shedding, also an actively regulated process linked to early anagen.
Throughout its life cycle the HF constantly regenerates via a myriad of stem cells of different lineages (primarily located in the “bulge”), and the “hair shaft factory”, the anagen hair bulb. As such the HF is also one of the most aging-resistant organs, with the notable exception of the pigmentary unit, whose failure to function initiates the graying process. Inflammation-induced damage to the bulge or destruction of bulge cells may produce permanent hair loss.
Mechanistic details which drive the HF cycle are still an open question5, although the circadian rhythm is thought to be associated with the process.
The length of the hair cycle stages varies dramatically in different parts of the human body. This has implications for maximal hair length.
The hair is a neuroendocrine organ and its growth is closely regulated by hormones, neuropeptides and signaling molecules, including melatonin, prolactin, thyrotropin-releasing hormone (TRH), thyrotropin (TSH), corticotropin-releasing hormone (CRH), proopiomelanocortin products such as alpha-melanocyte stimulating hormone (α-MSH), adrenocorticotropic hormone (ACTH), β-endorphin, catecholamines, and acetylcholine.
Various environmental factors such as day/night cycle duration, seasonal changes, emotional wellbeing and nutrient deficiencies may all significantly affect hair growth. Many of these effects will be mediated by neuroendocrine signalers.
Androgens (primarily testosterone and especially DHT) stimulate vellus HF’s to transform into larger, deeper follicles with longer, thicker, more pigmented hairs by binding to androgen receptors in the dermal papilla, causing alterations in gene expression. Not all hair is sensitive to androgens (e.g. the eyebrows) and in some regions (e.g. the scalp) the effect is opposite, causing hair to become thinner and less pigmented - this is the process of male-pattern baldness, aka androgenic alopecia.
In this way, HF’s pose a unique endocrine paradox as the same hormones cause both enlargement and inhibition of the same organ in different areas. These contrasts are explained by intrinsic differences in gene expression within follicles at different sites - this epigenetic programming occurs during the embryonic patterning processes.
Estrogens are used as treatment for androgen-dependent disorders, but their effects are probably due to interfering with androgen action rather than direct effects on HF’s. 17β-estradiol inhibits cultured human HF’s and rodent hair growth, stimulating catagen. On the other hand, during pregnancy hair growth is stimulated and the anagen phase is lengthened.
Progesterone and prolactin inhibit 5-αr (which converts testosterone to DHT). Prolactin inhibits hair shaft elongation and increases the keratinisation of hair (over which it has an important modulatory role).
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