Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 42, Pages 28835-28845Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.583450
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Funding
- National Research Foundation of Korea (NRF) [2012R1A5A1048236]
- Bio & Medical Technology Development Program Grant [2012M3A9B4028785]
- Redoxomics Grant - Ministry of Science, ICT & Future Planning [2012M3A9C5048708]
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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 ([Ca2+](i)) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of G(q) protein, IP3 generation, and [Ca2+](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.
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