The purpose of our study is to investigate the genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 (SRD5A1 and SRD5A2) genes in Korean population, and to study the association of these polymorphisms with the development, clinical types (female or male pattern) and therapeutic response of androgenetic alopecia.
Collectively, the enhanced expression of type II 5α-reductase, AR and Hic-5/ARA55 can upregulate sensitivity to androgen of dermal papilla cells in AGA.
DHT binds to the androgen receptor (AR) in scalp dermal papilla cells (DPC) to induce AR-mediated transcription of genes that contribute to AGA in genetically predisposed individuals.
Here, we analyze recent studies of androgens and AR roles in several skin-related disorders, focusing in the current understanding of their molecular mechanisms in androgenetic alopecia (AGA).
We demonstrate that genetic variability in the androgen receptor gene (AR) is the cardinal prerequisite for the development of early-onset AGA, with an etiological fraction of 0.46.
Furthermore, in the coculture of AR-overexpressing human dermal papilla cells from AGA and normal human keratinocytes, R1881 suppresses keratinocyte growth through androgen-inducible TGF-β1, indicating that TGF-β1 is one of the key players in pathogenesis of AGA.
The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)).
Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization.
Our recent findings indicate that the major AGA locus, an X-chromosome region containing the androgen receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common genetic factor underlying both early-onset FPHL and AGA.
We confirmed that the AR gene polymorphism (SNP rs6152 G>A) is associated with the development of AGA and higher PSA levels in patients with BPH but not cancer.
The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified.