Gpr173, also known as SREB3, is a highly conserved G protein-coupled receptor. It is associated with the hypothalamic-pituitary-gonadal reproductive axis and is expressed in the brain, ovaries, and other tissues [3]. Its ligand, phoenixin (PNX), mediates multiple biological functions through Gpr173, involving pathways like cAMP/PKA and MAPK p38, and is crucial for processes such as bone homeostasis, neural inhibitory regulation, and reproduction [1,2,3].

In MC3T3-E1 cells, Gpr173 signaling promotes osteoblastic differentiation. Its agonist phoenixin 20 induces the expression of osteoblast-related genes and matrix mineralization, and this effect is mediated by Runx2 and dependent on p38 MAPK activation. Silencing Gpr173 attenuates this differentiation, indicating its essential role in this process [1]. In the neocortex of mice, Gpr173, proposed as CCK3R, mediates the potentiation of GABAergic inhibition by CCK interneurons. This was demonstrated by the abolishment of inhibitory LTP in CCK knockout mice, highlighting its role in cortical excitation-inhibition balance [2].

In conclusion, Gpr173 is vital for regulating osteoblastic differentiation, which is crucial for bone homeostasis, and for mediating GABAergic inhibitory potentiation in the cortex, potentially related to brain disorders. Its role in the reproductive system, including folliculogenesis and regulation of the estrous cycle, also emphasizes its importance in reproductive health [1,2,3,4].

References:

1. Gu, Zhengtao, Xie, Denghui, Ding, Rui, Huang, Caiqiang, Qiu, Yiyan. 2020. GPR173 agonist phoenixin 20 promotes osteoblastic differentiation of MC3T3-E1 cells. In Aging, 13, 4976-4985. doi:10.18632/aging.103717. https://pubmed.ncbi.nlm.nih.gov/33196456/

2. He, Ling, Shi, Heng, Zhang, Ge, Yan, Hong, He, Jufang. 2023. A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 43, 2305-2325. doi:10.1523/JNEUROSCI.2035-22.2023. https://pubmed.ncbi.nlm.nih.gov/36813575/

3. McIlwraith, Emma K, Loganathan, Neruja, Belsham, Denise D. 2019. Regulation of Gpr173 expression, a putative phoenixin receptor, by saturated fatty acid palmitate and endocrine-disrupting chemical bisphenol A through a p38-mediated mechanism in immortalized hypothalamic neurons. In Molecular and cellular endocrinology, 485, 54-60. doi:10.1016/j.mce.2019.01.026. https://pubmed.ncbi.nlm.nih.gov/30716364/

4. Nguyen, Xuan Phuoc, Nakamura, Tomoko, Osuka, Satoko, Iwase, Akira, Kikkawa, Fumitaka. . Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis. In Reproduction (Cambridge, England), 158, 25-34. doi:10.1530/REP-19-0025. https://pubmed.ncbi.nlm.nih.gov/30933929/