title: Molecular mechanisms of androgenetic alopecia.
abstract: Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive thinning of the scalp hair that follows a defined pattern. While the genetic involvement is pronounced but poorly understood, major advances have been achieved in understanding principal elements of the androgen metabolism involved: androgen-dependent processes are predominantly due to the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell functions depend on the availability of weak androgens, their conversion to more potent androgens via the action of 5 alpha-reductase, low enzymatic activity of androgen inactivating enzymes, and functionally active AR present in high numbers. The predisposed scalp exhibits high levels of DHT, and increased expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a central role, while androgen-regulated factors deriving from dermal papilla cells are believed to influence growth of other components of the hair follicle. Current available treatment modalities with proven efficacy are oral finasteride, a competitive inhibitor of type 2 5 alpha-reductase, and topical minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has been reported to stimulate the production of vascular endothelial growth factor in cultured dermal papilla cells. Since the clinical success rate of treatment of AGA with modulators of androgen metabolism or hair growth promoters is limited, sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of AGA.
authors.affiliation: Department of Dermatology, University Hospital of Zurich, Gloriastr. 31, 8091 Zurich, Switzerland. ramitru@derm.unizh.ch
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Trüeb
mesh_terms: D000505:Alopecia / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D000728:Androgens / Q000502:physiology*; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D011944:Receptors, Androgen / Q000502:physiology
chemical_list: D000728:Androgens; D011944:Receptors, Androgen