Perifollicular fibrosis: pathogenetic role in androgenetic alopecia.
Androgenetic alopecia (AGA) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10(-9)-10(-7) M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10(-8) M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-beta1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-beta1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-beta1 antibody (10 microg/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-beta1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the AGA, and the inhibitory effects on T-induced procollagen and TGF-beta1 expression may explain another possible mechanism how finasteride works in AGA.
Yoo
Hyeon Gyeong
HG
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, and Institute of Dermatological Science, Seoul National University, Seoul, Korea.
Kim
Jin Sook
JS
Lee
Se Rah
SR
Pyo
Hyun Keol
HK
Moon
Hyung In
HI
Lee
Jong Hee
JH
Kwon
Oh Sang
OS
Chung
Jin Ho
JH
Kim
Kyu Han
KH
Eun
Hee Chul
HC
Cho
Kwang Hyun
KH
D000505:Alopecia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D018120:Finasteride / Q000494:pharmacology; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D013739:Testosterone; D018120:Finasteride