Min Sun1, Hong-Fu Xie1, Yan Tang1, Shang-Qing Lin1, Jin-Mao Li1, Shu-Na Sun2, Xing-Lin Hu3, Ying-Xue Huang1, Wei Shi1, Dan Jian4. 1. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. 2. Shangdong University of TCM, Shangdong, China. 3. Department of Dermatology, First People's Hospital of Chenzhou City, Chenzhou, Hunan, China. 4. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. Electronic address: 569085332@qq.com.
Abstract
OBJECTIVE: This study investigated the role and mechanism of action of G protein-coupled estrogen receptor (GPER) in melanogenesis. METHODS: GPER expression was detected in the A375 human melanoma cell line and B16 mouse melanoma cell line. Cell proliferation, melanin content, tyrosinase (TYR) activity, cyclic adenosine monophosphate (cAMP) level, and TYR and microphthalmia-related transcription factor (MITF) expression were measured. GPER activation was altered by agonist and antagonist treatment and its expression was downregulated by gene silencing. Estradiol-induced melanin synthesis and the activation of related signaling pathways were suppressed by inhibiting GPER via antagonist treatment. The relationship between GPER and TYR was evaluated in clinical chloasma samples by immunohistochemistry. RESULTS: Upregulation of GPER in A375 cells promoted melanogenesis, favored as indicated by increases in TYR and MITF expression and TYR activity. GPER activated melanin production via the cAMP-protein kinase (PK) A pathway, suggesting that GPER plays an important role in estrogen-induced melanin synthesis. The effect of GPER activation on cAMP-MITF-TYR signaling was also demonstrated in B16 cells. A significant association was observed between GPER and TYR expression in chloasma skin lesions relative to normal skin. CONCLUSION: GPER enhances melanin synthesis via cAMP-PKA-MITF-TYR signaling and modulates the effects of estrogen in melanogenesis. GPER is therefore a potential drug target for chloasma treatment. Copyright Â
OBJECTIVE: This study investigated the role and mechanism of action of G protein-coupled estrogen receptor (GPER) in melanogenesis. METHODS:GPER expression was detected in the A375 humanmelanoma cell line and B16 mousemelanoma cell line. Cell proliferation, melanin content, tyrosinase (TYR) activity, cyclic adenosine monophosphate (cAMP) level, and TYR and microphthalmia-related transcription factor (MITF) expression were measured. GPER activation was altered by agonist and antagonist treatment and its expression was downregulated by gene silencing. Estradiol-induced melanin synthesis and the activation of related signaling pathways were suppressed by inhibiting GPER via antagonist treatment. The relationship between GPER and TYR was evaluated in clinical chloasma samples by immunohistochemistry. RESULTS: Upregulation of GPER in A375 cells promoted melanogenesis, favored as indicated by increases in TYR and MITF expression and TYR activity. GPER activated melanin production via the cAMP-protein kinase (PK) A pathway, suggesting that GPER plays an important role in estrogen-induced melanin synthesis. The effect of GPER activation on cAMP-MITF-TYR signaling was also demonstrated in B16 cells. A significant association was observed between GPER and TYR expression in chloasma skin lesions relative to normal skin. CONCLUSION:GPER enhances melanin synthesis via cAMP-PKA-MITF-TYR signaling and modulates the effects of estrogen in melanogenesis. GPER is therefore a potential drug target for chloasma treatment. Copyright Â
Authors: Jang Hoon Kim; Hyo Young Kim; Si Yong Kang; Jin-Baek Kim; Young Ho Kim; Chang Hyun Jin Journal: Molecules Date: 2018-01-22 Impact factor: 4.411
Authors: Christopher A Natale; Jinyang Li; Junqian Zhang; Ankit Dahal; Tzvete Dentchev; Ben Z Stanger; Todd W Ridky Journal: Elife Date: 2018-01-16 Impact factor: 8.140
Authors: You Chul Chung; Seoyeon Kim; Jin Hwa Kim; Geun Soo Lee; Jung No Lee; Nam Ho Lee; Chang-Gu Hyun Journal: Molecules Date: 2017-10-11 Impact factor: 4.411