Gper1, also known as GPR30, is a G-protein-coupled estrogen receptor. It binds 17-β-estradiol with high affinity and is involved in non-genomic estrogen signaling, rapidly activating kinase cascades and calcium flux within cells [5]. It has a wide-ranging impact on various biological processes, including cell proliferation, apoptosis, and social behaviors, and is relevant to multiple physiological and pathological conditions [2,3,5]. Genetic models, such as knockout (KO) mouse models, are valuable for studying its functions.

In multiple myeloma, GPER1 mRNA is down-regulated in plasma cells from patients, and lower expression associates with worse overall survival. The pharmacological activation of GPER1 using the agonist G-1 triggers anti-MM activity through apoptosis induction and reduces in vivo MM growth in xenograft models [1]. In a UUO-induced renal fibrosis model, G-1 treatment in ovariectomized female and male mice led to fewer renal fibrotic lesions and less macrophage infiltration, while Gper1 deletion in male UUO mice accelerated renal fibrosis [4]. In MC3T3-E1 cells (osteoblast precursors), T3-induced osteogenesis was mediated by GPER1-mediated glycolysis, as treatment with a GPER1-specific antagonist reversed T3-promoted osteogenesis-related activity [6]. In GPER1-KO mice, there were sex-specific effects on hippocampal plasticity and cognitive function, with males showing reduced anxiety and females showing increased fear response, along with impaired spatial learning and memory in both sexes [7].

In conclusion, Gper1 plays crucial roles in multiple biological processes and diseases. Through the use of KO mouse models, its functions in cancer (such as multiple myeloma), renal fibrosis, osteogenesis, and hippocampal-related cognitive functions have been revealed. Understanding Gper1 can potentially provide new therapeutic targets for these diseases.

References:

1. Gallo Cantafio, Maria Eugenia, Torcasio, Roberta, Scionti, Francesca, Viglietto, Giuseppe, Amodio, Nicola. 2023. GPER1 Activation Exerts Anti-Tumor Activity in Multiple Myeloma. In Cells, 12, . doi:10.3390/cells12182226. https://pubmed.ncbi.nlm.nih.gov/37759449/

2. Vivacqua, Adele. 2020. GPER1 and microRNA: Two Players in Breast Cancer Progression. In International journal of molecular sciences, 22, . doi:10.3390/ijms22010098. https://pubmed.ncbi.nlm.nih.gov/33374170/

3. Dovey, Janine L, Vasudevan, Nandini. 2020. Does GPER1 Play a Role in Sexual Dimorphism? In Frontiers in endocrinology, 11, 595895. doi:10.3389/fendo.2020.595895. https://pubmed.ncbi.nlm.nih.gov/33193108/

4. Xie, Lin, Cheng, Ye, Du, Wen, Chen, Min, Gu, Xiangchen. 2023. Activation of GPER1 in macrophages ameliorates UUO-induced renal fibrosis. In Cell death & disease, 14, 818. doi:10.1038/s41419-023-06338-2. https://pubmed.ncbi.nlm.nih.gov/38086848/

5. Hadjimarkou, Maria M, Vasudevan, Nandini. 2017. GPER1/GPR30 in the brain: Crosstalk with classical estrogen receptors and implications for behavior. In The Journal of steroid biochemistry and molecular biology, 176, 57-64. doi:10.1016/j.jsbmb.2017.04.012. https://pubmed.ncbi.nlm.nih.gov/28465157/

6. Xue, Ying, Liu, Guo-Ming, Ke, Dian-Shan, Yu, Yun-Long, Hou, Jian-Ming. 2023. GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors. In Experimental biology and medicine (Maywood, N.J.), 248, 1732-1744. doi:10.1177/15353702231198067. https://pubmed.ncbi.nlm.nih.gov/37750023/

7. Koitmäe, Aune, Karsten, Yannik, Li, Xiaoyu, Rune, Gabriele M, Bender, Roland A. 2023. GPER1 deficiency causes sex-specific dysregulation of hippocampal plasticity and cognitive function. In The Journal of endocrinology, 258, . doi:10.1530/JOE-22-0204. https://pubmed.ncbi.nlm.nih.gov/37399525/