Androgen regulation of the human hair follicle: the type I hair keratin hHa7 is a direct target gene in trichocytes.
Previous work had shown that most members of the complex human hair keratin family were expressed in terminal scalp hairs. An exception to this rule was the type I hair keratin hHa7, which was only detected in some but not all vellus hairs of the human scalp (Langbein et al, 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual hairs. Medullated beard, axillary, and pubic hairs arise during puberty from small, unmedullated vellus hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG(A)/(T)ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on hair follicles and might be a suitable tool for investigations of androgen-dependent hair disorders.
Jave-Suarez
Luis F
LF
Section of Normal and Neoplastic Epidermal Differentiation, German Cancer Research Center, Heidelberg, Germany.
Langbein
Lutz
L
Winter
Hermelita
H
Praetzel
Silke
S
Rogers
Michael A
MA
Schweizer
Juergen
J
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D011944:Receptors, Androgen / Q000032:analysis / Q000502:physiology; D020218:Response Elements; D014158:Transcription, Genetic
D000728:Androgens; D011944:Receptors, Androgen; D007633:Keratins