GPR101, an orphan G protein-coupled receptor belonging to Family A rhodopsin-like family, is predominantly expressed in the hypothalamus and pituitary. It is actively involved in energy homeostasis and is crucial in regulating functions like energy balance and reproduction [1,2]. GPR101 couples to Gαs, Gαi, Gq/11 and G12/13 proteins and is associated with the regulation of the hypothalamus-pituitary-gonad axis [1].

In transgenic mice with elevated somatotrope Gpr101 expression (GhrhrGpr101), Gpr101 causes elevated GH/prolactin secretion without hyperplasia/tumorigenesis, indicating its role in the regulation of the somatotrope axis function [4]. In macrophages, GPR101 knockdown limited the ability of RvD5n-3 DPA to upregulate cyclic adenosine monophosphate, phagocytosis of bacteria, and efferocytosis, suggesting its role in mediating the leukocyte-directed actions of RvD5n-3 DPA [3].

In conclusion, GPR101 plays essential roles in energy homeostasis, regulation of the somatotrope axis, and mediating leukocyte-directed actions. The study of Gpr101 through mouse models has provided insights into its functions in growth-related and inflammatory processes, which may be relevant to understanding diseases such as X-linked acrogigantism and inflammatory arthritis [1,3,4].

References:

1. Hou, Zhi-Shuai, Tao, Ya-Xiong. 2018. Mutations in GPR101 as a potential cause of X-linked acrogigantism and acromegaly. In Progress in molecular biology and translational science, 161, 47-67. doi:10.1016/bs.pmbts.2018.10.003. https://pubmed.ncbi.nlm.nih.gov/30711029/

2. Yang, Zhao, Wang, Jun-Yan, Yang, Fan, Gao, Ning, Sun, Jin-Peng. 2023. Structure of GPR101-Gs enables identification of ligands with rejuvenating potential. In Nature chemical biology, 20, 484-492. doi:10.1038/s41589-023-01456-6. https://pubmed.ncbi.nlm.nih.gov/37945893/

3. Flak, Magdalena B, Koenis, Duco S, Sobrino, Agua, Palmas, Francesco, Dalli, Jesmond. . GPR101 mediates the pro-resolving actions of RvD5n-3 DPA in arthritis and infections. In The Journal of clinical investigation, 130, 359-373. doi:10.1172/JCI131609. https://pubmed.ncbi.nlm.nih.gov/31793912/

4. Abboud, Dayana, Daly, Adrian F, Dupuis, Nadine, Beckers, Albert, Hanson, Julien. 2020. GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11. In Nature communications, 11, 4752. doi:10.1038/s41467-020-18500-x. https://pubmed.ncbi.nlm.nih.gov/32958754/