Proliferation, DNA repair and apoptosis in androgenetic alopecia.
BACKGROUND
Androgenetic alopecia is a common hair disorder, resulting from interplay of genetic, endocrine and ageing factors. Meanwhile, it is unclear if an altered degree of proliferation or increased apoptosis could contribute to its pathogenesis.


OBJECTIVE
To evaluate the role of proliferation, DNA damage and apoptosis in the pathogenesis of androgenetic alopecia.


METHODS
Thirty biopsies were taken from the frontal (bald) area and occipital (hairy) area of 15 male patients with androgenetic alopecia, as well as five specimens from frontal area of five age-matched controls. These specimens were used for immunohistochemical staining of cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA repair markers (XRCC1, APE1, PARP-1) as well as apoptosis regulatory protein p53.


RESULTS
The frontal bald area of patients showed significantly higher levels of X-ray Cross Complementing-1 (XRCC1; P<0.001) and p53 (P<0.001) expression when compared with occipital hairy area of patients and frontal area of controls (P=0.003 and 0.04, respectively). On the other hand, there were significantly lower expression of PCNA (P<0.001) and apurinic/apyridinic endonuclease 1 (APE1; P=0.001 and 0.02) when compared with the frontal area of controls and occipital area of patients, respectively. Meanwhile, APE1 showed significant inverse correlation with p53 overexpression (P=0.03).


CONCLUSIONS
The frontal bald area of patients with androgenetic alopecia has lower proliferation rate that result in follicular miniaturization. There is increased DNA damage that would be beyond the capacity of cells to repair in advanced cases. An alternative pathway would take place in order to eliminate the damaged cells through apoptosis.
El-Domyati
M
M
Department of Dermatology, Faculty of Medicine, Al-Minya University, Al-Minya, Egypt. moetazeldomyati@yahoo.com
Attia
S
S
Saleh
F
F
Bassyouni
M I
MI
El-Fakahany
H
H
Abdel-Wahab
H
H
D000328:Adult; D000505:Alopecia / Q000235:genetics* / Q000473:pathology*; D000728:Androgens / Q000502:physiology*; D017209:Apoptosis; D049109:Cell Proliferation; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D000728:Androgens; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase