The Hair Follicle: A Paradoxical Androgen Target Organ

Abstract

Androgens are the main regulator of normal human hair growth. After puberty, they promote transformation of vellus follicles, producing tiny, unpigmented hairs, to terminal ones, forming larger pigmented hairs, in many areas, e.g. the axilla. However, they have no apparent effect on the eyelashes, but can cause the opposite transformation on the scalp leading to the replacement of terminal hairs by vellus ones and the gradual onset of androgenetic alopecia. This paradox appears to be an unique hormonal effect. Hair follicles are mainly epithelial tissues, continuous with the epidermis, which project into the dermis. A mesenchyme-derived dermal papilla enclosed within the hair bulb at the base controls many aspects of follicle function. In the current hypothesis for androgen regulation, the dermal papilla is also considered the main site of androgen action with androgens from the blood binding to receptors in dermal papilla cells of androgen-sensitive follicles and causing an alteration of their production of paracrine factors for target cells e.g. keratinocytes. Studies of cultured dermal papilla cells from sites with different responses to androgens in vivo have confirmed the paradoxical responses. All dermal papilla cells from androgen-sensitive sites contain low capacity, high affinity androgen receptors. However, only some cells formed 5α-dihydrotestosterone, e.g. beard but not axillary cells, in line with hair growth in 5α-reductase deficiency. Incubation with androgens also stimulated the mitogenic capacity of beard cell media, but inhibited that produced by scalp cells. This suggests that the paradoxical differences are due to differential gene expression within hair follicles, presumably caused during embryogenesis.

Long Eyelashes in a Case Series of 93 Children With Vernal Keratoconjunctivitis

“…Androgens are the principal hormones that control sexual hair growth by receptors localized in the dermal papilla, 20 but eyelashes seem not to be sensitive. 21 Retinoic acid derivatives affect the hair growth cycle in mice by increasing the length of the anagen phase, and insulin-like growth factor-I slows the hair cycle entry in the catagen phase; growth hormone, insulin, glycocorticoids, and prolactin are also implicated, but there is no evidence to support an involvement of these hormones in eyelash growth. 19 Excessive growth of eyelashes (trichomegaly) has been reported in some congenital and acquired conditions.…”

The Hair Follicle as an Estrogen Target and Source

“…Estrogens and estrogen metabolism are at least as important as androgens in male and female hair biology. Androgens are recognized key regulators of normal human hair growth and the prerequisite for sexual hair and sebaceous gland development (21,22). However, estrogens also profoundly alter hair growth in practically all mammalian species investigated and operate as key modulators of hair follicle biology by binding to high-affinity cognate receptors (ERs) (19,(23)(24)(25)(26)(27)(28).…”

EEMCO Guidance for the Assessment of Hair Shedding and Alopecia

“…It is taken for granted that androgens alone or in combination with other mediators are the main regulators of normal hair growth [38,39]. However, regional variability of the human hair response is large according to the body site.…”