title: Testosterone stimulates Duox1 activity through GPRC6A in skin keratinocytes.
abstract: Testosterone is an endocrine hormone with functions in reproductive organs, anabolic events, and skin homeostasis. We report here that GPRC6A serves as a sensor and mediator of the rapid action of testosterone in epidermal keratinocytes. The silencing of GPRC6A inhibited testosterone-induced intracellular calcium ([Ca(2+)]i) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of Gq protein, IP3 generation, and [Ca(2+)]i mobilization, leading to Duox1 activation. H2O2 generation by testosterone stimulated the apoptosis of keratinocytes through the activation of caspase-3. The application of testosterone into three-dimensional skin equivalents increased the apoptosis of keratinocytes between the granular and stratified corneum layers. These results support an understanding of the molecular mechanism of testosterone-dependent apoptosis in which testosterone stimulates H2O2 generation through the activation of Duox1.
authors.affiliation: From the Department of Life Science and GT5 program, Ewha Womans University.
authors.forename: Eunbi
authors.initials: E
authors.lastname: Ko
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, 446-729 and.
authors.forename: Hyun
authors.initials: H
authors.lastname: Choi
authors.affiliation: From the Department of Life Science and GT5 program, Ewha Womans University.
authors.forename: Borim
authors.initials: B
authors.lastname: Kim
authors.affiliation: From the Department of Life Science and GT5 program, Ewha Womans University.
authors.forename: Minsun
authors.initials: M
authors.lastname: Kim
authors.affiliation: From the Department of Life Science and GT5 program, Ewha Womans University.
authors.forename: Kkot-Nara
authors.initials: KN
authors.lastname: Park
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, 446-729 and.
authors.forename: Il-Hong
authors.initials: IH
authors.lastname: Bae
authors.affiliation: the Department of Immunology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Young Kwan
authors.initials: YK
authors.lastname: Sung
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, 446-729 and.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, 446-729 and biopang@amorepacific.com.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
authors.affiliation: From the Department of Life Science and GT5 program, Ewha Womans University, baeys@ewha.ac.kr.
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D000074623:Dual Oxidases; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000737:chemistry*
chemical_list: C488584:GPRC6A protein, human; D043562:Receptors, G-Protein-Coupled; D013739:Testosterone; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D002118:Calcium
keywords: Apoptosis; Cell Signaling; NADPH Oxidase; Reactive Oxygen Species (ROS); Testosterone