PMID- 25838072 OWN - NLM STAT- MEDLINE DCOM- 20160204 LR - 20211203 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 757 DP - 2015 Jun 15 TI - Effects of dihydrotestosterone on rat dermal papilla cells in vitro. PG - 74-83 LID - S0014-2999(15)00284-8 [pii] LID - 10.1016/j.ejphar.2015.03.055 [doi] AB - 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-beta (TGF-beta) 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 beta-catenin, an important regulator of hair growth and proliferation, while lithium chloride, a glycogen synthase kinase-3beta inhibitor, attenuated the DHT-induced downregulation of the beta-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 beta-catenin level, and upregulating the TGF-beta/Smad and HSP27 level, whereas activation of mTOR by DHT could attenuate the inhibition of hair growth cycle in immortalized DPCs. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Kang, Jung-Il AU - Kang JI AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Kim, Sang-Cheol AU - Kim SC AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Kim, Min-Kyoung AU - Kim MK AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Boo, Hye-Jin AU - Boo HJ AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Kim, Eun-Ji AU - Kim EJ AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Im, Guang-Jin AU - Im GJ AD - Research and Development Center, Samchundang Pharmaceutical Co. Ltd., Yeongtong-Gu, Seoul 443-270, Republic of Korea. FAU - Kim, Young Ho AU - Kim YH AD - College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. FAU - Hyun, Jin-Won AU - Hyun JW AD - Department of Biochemistry, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Kang, Ji-Hoon AU - Kang JH AD - Department of Neurology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Koh, Young-Sang AU - Koh YS AD - Department of Microbiology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Park, Deok-Bae AU - Park DB AD - Department of Histology, School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Yoo, Eun-Sook AU - Yoo ES AD - Department of Pharmacology School of Medicine, Institute of Medical Sciences, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Republic of Korea. FAU - Kang, Hee-Kyoung AU - Kang HK AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150330 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Carrier Proteins) RN - 0 (Eif4ebp1 protein, rat) RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoproteins) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Transcription Factor RelA) RN - 0 (Transforming Growth Factor beta) RN - 0 (beta Catenin) RN - 08J2K08A3Y (Dihydrotestosterone) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Active Transport, Cell Nucleus/drug effects MH - Animals MH - Carrier Proteins/metabolism MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Nucleus/drug effects/metabolism MH - Cyclooxygenase 2/metabolism MH - Dihydrotestosterone/*pharmacology MH - HSP27 Heat-Shock Proteins/metabolism MH - Hair Follicle/*cytology/*drug effects/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Phosphoproteins/metabolism MH - Phosphorylation/drug effects MH - Rats MH - Smad2 Protein/metabolism MH - Smad3 Protein/metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Transcription Factor RelA/metabolism MH - Transforming Growth Factor beta/metabolism MH - beta Catenin/metabolism OTO - NOTNLM OT - Dihydrotestosterone OT - Heat shock protein 27 OT - Immortalized dermal papilla cells OT - TGF-beta/Smad OT - mTOR OT - beta-catenin EDAT- 2015/04/04 06:00 MHDA- 2016/02/05 06:00 CRDT- 2015/04/04 06:00 PHST- 2015/02/17 00:00 [received] PHST- 2015/03/11 00:00 [revised] PHST- 2015/03/17 00:00 [accepted] PHST- 2015/04/04 06:00 [entrez] PHST- 2015/04/04 06:00 [pubmed] PHST- 2016/02/05 06:00 [medline] AID - S0014-2999(15)00284-8 [pii] AID - 10.1016/j.ejphar.2015.03.055 [doi] PST - ppublish SO - Eur J Pharmacol. 2015 Jun 15;757:74-83. doi: 10.1016/j.ejphar.2015.03.055. Epub 2015 Mar 30.