Testosterone stimulates Duox1 activity through GPRC6A in skin keratinocytes

Eunbi Ko, Hyun Choi, Borim Kim, Minsun Kim, Kkot Nara Park, Il Hong Bae, Young Kwan Sung, Tae Ryong Lee, Dong Wook Shin, Yun Soo Bae

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 ofGPRC6Ainhibited testosterone-induced intracellular calcium ([Ca2+]i) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of Gq 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.

Original languageEnglish
Pages (from-to)28835-28845
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number42
DOIs
StatePublished - 17 Oct 2014

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