title: Effects of dihydrotestosterone on rat dermal papilla cells in vitro.
abstract: Androgenetic alopecia involves the action of dihydrotestosterone (DHT) on dermal papilla cells (DPCs) that line the base of the hair follicle. However, the mechanism of DHT action is not completely understood. The effects of DHT on DPCs, regulatory cells that function in follicle growth and the hair cycle, were examined in immortalized cells derived from rat vibrissa follicles. DHT did not affect the proliferation of immortalized DPCs. However, flow cytometry analysis revealed that DHT increased cell-cycle arrest in these cells, which was accompanied by an increase in the p27(kip1) level and by decreases in cyclin E, cyclin D1, and cyclin-dependent kinase 2 levels. DHT treatment resulted in the phosphorylation and nuclear translocation of Smad2/3, a mediator of the transforming growth factor-β (TGF-β) signaling pathway, which leads to the catagen phase of the hair cycle. DHT also induced the phosphorylation and nuclear translocation of heat shock protein 27 (HSP27). Moreover, DHT decreased the levels of total and nuclear β-catenin, an important regulator of hair growth and proliferation, while lithium chloride, a glycogen synthase kinase-3β inhibitor, attenuated the DHT-induced downregulation of the β-catenin level. On the other hand, DHT increased the phosphorylation of mammalian target of rapamycin (mTOR), a regulator of proliferation, in immortalized DPCs. These results illustrate that DHT could shorten the duration of the hair growth cycle by initiating cell-cycle arrest, downregulating the β-catenin level, and upregulating the TGF-β/Smad and HSP27 level, whereas activation of mTOR by DHT could attenuate the inhibition of hair growth cycle in immortalized DPCs.
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Kang
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Boo
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Research and Development Center, Samchundang Pharmaceutical Co. Ltd., Yeongtong-Gu, Seoul 443-270, Republic of Korea.
authors.forename: Guang-Jin
authors.initials: GJ
authors.lastname: Im
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Neurology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Microbiology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Koh
authors.affiliation: Department of Histology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Deok-Bae
authors.initials: DB
authors.lastname: Park
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
authors.affiliation: Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. Electronic address: pharmkhk@jejunu.ac.kr.
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D055551:HSP27 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D013196:Dihydrotestosterone; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: Dihydrotestosterone; Heat shock protein 27; Immortalized dermal papilla cells; TGF-β/Smad; mTOR; β-catenin