Molecular Genetic and Endocrine Mechanisms of Hair Growth

Abstract

The prenatal morphogenesis of hair follicles depends upon a precisely regulated series of molecular genetic processes. Hormones and their receptors play prominent roles in modulating postnatal hair cycling, which recapitulates some aspects of morphogenesis. The responses to androgen are the most obvious of these. The postnatal androgen sensitivity of pilosebaceous units in different skin areas is programmed during prenatal development to permit clinical outcomes such as hirsutism and pattern baldness. Thyroid hormone, glucocorticoids, insulin-like growth factor-I, and prolactin have clinically significant effects on specific aspects of hair growth. The nuclear receptors vitamin D receptor and retinoid X receptor are essential for postnatal hair cycling. Other hormones have less clear effects on hair growth. Advances in research on the interaction of hormone target genes with the biological processes involved in hair morphogenesis and cycling can be expected to improve management of hirsutism and alopecia.

The Hair Follicle as an Estrogen Target and Source

“…1); they can repopulate both the hair follicle and the interfollicular epidermis (60). Bulge cells are slowly cycling and are quiescent until they receive a signal to leave their niche and begin dividing and differentiating to support a new anagen or to repopulate a skin defect (61,62).…”

“…• How are ER expression and intrafollicular E2 synthesis/ metabolism regulated? • Given that the pilosebaceous unit itself is a formidable source of estrogen synthesis both in men and women that displays substantial aromatase activity (61), which percentage of circulating estrogens is provided by peripheral estrogen synthesis in the skin under physiological and pathological conditions, and how much of this intracutaneous estrogen synthesis arises from the pilosebaceous unit (hair follicle vs. sebaceous gland)? • Within the puzzling maze of interaction possibilities that one, theoretically, needs to consider when asking how E2 may mediate its effects on human hair follicle growth and cycling (see above), which are the key interactions and signaling cross talks that really matter most, whose pharmacological manipulation promises the best therapeutical effects in the management of hair loss disorders?…”

Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

“…PRL has been shown to stimulate hair growth, moulting, and shedding in sheep and mink, and contradictory data report of induction of both anagen (hair growth) and catagen (HF regression) in seasonal dependent HFs by PRL. [13][14][15][16][17][18] Although PRL and melatonin stimulate hair shaft elongation in culture in cashmere goats, 16 increased levels of PRL after experimentally increased photoperiods have been shown to decrease hair growth in vitro. 7,19 Increasing PRL levels in spring was even shown to reactivate telogen HFs and induce anagen in cashmere goats.…”

Epithelium-Mesenchyme Interactions Control the Activity of Peroxisome Proliferator-Activated Receptor β/δ during Hair Follicle Development

“…In addition, many members of the nuclear receptor family, including the estrogen (NR3A), vitamin D (NR1I), and retinoid receptors (NR1B and NR2B), have been identified as important modulators of skin as well as HF development and homeostasis, both in humans and mice (1,23). Recent reports also suggest a role for peroxisome proliferator-activated receptor (PPAR) in fetal epidermal development, particularly keratinocyte and sebocyte differentiation in rodents (5,29,39).…”